Specific and long-lasting suppression of rat adjuvant arthritis by low-dose Mycobacterium butyricum

The thyrotropin-releasing hormone (TRH) analog, RX 77368, (p-Glu-His-(3,3'-dimethyl)-Pro-NH2) injected intracisternally (i.c.) at low doses increases gastric mucosal blood flow through vagal cholinergic and calcitonin gene-related peptide dependent pathways. The influence of the mast cell stabilizer, ketotifen, on i.c. injection of RX 77368 (1.5 ng)-induced changes in gastric mucosal blood flow (hydrogen gas-clearance technique), gastric acid secretion and mean arterial pressure was studied in urethane-anesthetized rats. RX 77368 increased gastric blood flow by 131% and systemic arterial pressure by 11 mm Hg and decreased gastric mucosal vascular resistance by 54% whereas acid secretion was not altered within the 30 min period post injection. Ketotifen had no effect on these basal parameters but abolished i.c. RX 77368-induced increased gastric mucosal blood flow and decreased gastric vascular resistance. These data suggest that mast cells may be part of the peripheral mechanisms involved in vagal gastric hyperemia induced by TRH analog injected i.c. at a low dose.     

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline-TRH, in healthy volunteers

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.     

Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats

Cold exposure increases TRH gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We investigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor (TRHr) antisense oligodeoxynucleotides (100 microg twice, -48 and -24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 microg) or the somatostatin subtype 5-preferring analog, BIM-23052 (1 microg), injected intracisternally increased basal gastric emptying by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BIM-23052. Cold exposure increased gastric emptying by 64%, and the response was inhibited by vagotomy, atropine (0.1 mg/kg, i.p.), and TRHr antisense (intracisternally). Saline or mismatched oligodeoxynucleotides, injected intracisternally under similar conditions, did not alter the enhanced gastric emptying induced by cold or intracisternal injection of TRH or BIM-23052. These results indicate that TRH receptor activation in the brain stem mediates acute cold-induced vagal cholinergic stimulation of gastric transit, and that medullary TRH may play a role in the autonomic visceral responses to acute cold.     

Central effect of melatonin against stress-induced gastric ulcers in rats

We investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.     

Intracerebroventricular CRF inhibits cold restraint-induced c-fos expression in the dorsal motor nucleus of the vagus and gastric erosions in rats

Acute exposure to cold-restraint induces vagal-dependent gastric erosions associated with activation of neurons in the dorsal motor nucleus of the vagus (DMN) in rats. The influence of intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) (10 micrograms) on c-fos expression in the brain and gastric erosions induced by 3 h cold-restraint was investigated in conscious rats. In cold-restraint exposed rats, CRF injected i.c.v. inhibited gastric erosions and the number of Fos positive neurons in the DMN by 93 and 72%, respectively, while Fos labelling in the nucleus tractus solitarius (NTS) was increased by 5-fold compared with vehicle group. c-fos expression was also induced in the central amygdala by i.c.v. CRF, unlike the vehicle-injected group exposed to cold-restraint. c-fos expression induced by cold-restraint in the raphe pallidus (Rpa) and paraventricular nucleus of the hypothalamus was not altered by i.c.v. CRF. These data indicate that central CRF-induced gastric protection results from the inhibition of DMN neuronal activity enhanced by cold-restraint. CRF action on DMN neurons may be related to the increase in the NTS and central amygdala inputs leading to inhibition of DMN neurons rather than to the decrease in the excitatory input from the caudal raphe projections to the DMN.     

Spiral CT: applications in the emergency patient

The influence of vasopressin (AVP) on recall of information in a passive avoidance situation after bilateral 6-OHDA lesions to the central amygdala was tested. AVP given 15 min before the retention testing at the icv dose of 1 microgram significantly prolonged avoidance latencies both in lesioned and in sham-operated rats in comparison with the respective icv saline injected animals. Insignificant increase of spontaneous locomotor activity in rats lesioned to the central amygdala was unlikely to interfere with the cognitive effect of AVP. These results suggest that dopaminergic projection to the central amygdala is not responsible for the facilitatory effect of AVP on retrieval process in a passive avoidance situation.     

Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: studies on two immortal colon cancer cell lines

Brain corticotropin-releasing factor (CRF) is involved in stress-related alterations of gastric acid secretion. CRF in the locus coeruleus has been shown to induce anxiogenic behavioral responses and to mimic stress-induced alterations of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric acid secretion was investigated in urethane-anesthetized gastric fistula rats. In sham-operated animals, CRF (126-420 pmol) microinfused bilaterally into the LC/SC induced a dose-dependent inhibition of pentagastrin (PG)-stimulated gastric acid secretion of 60-81% within the first hour after microinjection. At the 420 pmol dose, this inhibitory effect of CRF into the LC/SC lasted throughout the whole observation period of 120 min. After bilateral vagotomy, basal and PG-stimulated gastric acid secretion at microinjection of vehicle was reduced. Nevertheless, microinfusion of 420 pmol CRF into the LC/SC still inhibited significantly gastric acid secretion by 62.1%. In contrast, in spinal cord transected animals bilateral microinfusion of 420 pmol CRF into the LC/SC did not reduce PG-stimulated gastric acid secretion. These data indicate that CRF acts in the LC/SC to induce a long lasting inhibition of peripherally stimulated gastric acid secretion via spinal pathways. These findings suggest a possible role of the LC/SC in the regulation of gastric secretion and of endogenous CRF at these sites in the stress-related inhibition of gastric acid secretion by affecting autonomic nervous system activity.     

Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms

This study investigated effects of glucagon-like peptide-1(7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractility of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmol/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.     

Different effects of indomethacin and nabumetone on prostaglandin-mediated gastric responses to central vagal activation in rats

Intracisternal injection of a stable thyrotropin-releasing hormone (TRH) analog increases gastric prostaglandins release and mucosal resistance to injury through central vagal pathways. The effects of two nonsteroidal anti-inflammatory drugs, indomethacin (INDO) and nabumetone on intracisternal injection of various doses of TRH-induced gastric acid secretion and changes in mucosal resistance were investigated in urethane-anesthetized rats. Doses of INDO (5 mg/kg) and nabumetone (13.75 mg/kg) producing similar acute anti-inflammatory response in the carrageenin-induced paw edema were injected i.p. in all studies. INDO potentiated the acid secretion induced by intracisternal injection of TRH at 25, 50 and 200 ng by 5.1-, 1.9- and 1.4-fold, respectively, whereas nabumetone did not modify the secretory response to TRH. Moderate erosions were observed in 100% of rats treated with the combination of INDO and TRH (200 ng) whereas no erosions were observed when TRH or INDO were given alone or TRH in combination with nabumetone. TRH at 7 ng reduced mucosal damage induced by intragastric administration of ethanol (60%, 1 ml/kg) by 63%. The mucosal protective action of TRH was abolished by INDO but not altered by nabumetone pretreatment. These data indicate that at comparable anti-inflammatory doses, nabumetone, unlike INDO, neither blocks the protection against ethanol injury induced by low doses of TRH injected intracisternally nor potentiates the gastric acid secretion or lesions induced by higher dose of TRH. We speculate that these differences reflect reduced inhibition of gastric prostaglandins by nabumetone.     

Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats.

A unilateral microinjection of morphine into the amygdala impaired the acquisition of fear and hypoalgesic responses in rats exposed to a heated floor in a hot-plate apparatus. This impairment was dose dependent, receptor specific, and not observed in rats microinjected with morphine into the caudal basolateral amygdala. A microinjection of morphine into the amygdala reduced the expression of fear responses and of naloxone-sensitive hypoalgesic responses, but did not reduce the expression of naloxone-insensitive hypoalgesic responses. The results document an involvement of opioidergic mechanisms in the amygdala in learned danger and of the amygdala in the control of opioid hypoalgesic responses. They also suggest that learned danger can activate antinociceptive mechanisms independently of the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission

Unilateral microinjection of neurotensin in the ventral tegmental area of the rat (2.5 micrograms/0.5 microliter) produced behavioural excitation illustrated by contralateral circling. Given orally, SR 48692, a selective and potent non-peptide neurotensin receptor antagonist, significantly reduced these rotations with a triphasic dose-effect relationship. Inhibition occurred at 0.12 mg/kg; further increases in dose up to 2.5 mg/kg produced no significant antagonism, then at doses > or = 5 mg/kg, a second phase of antagonism was observed. Bilateral injection of neurotensin (0.5 microgram each side) into the nucleus accumbens antagonized the increase in locomotor activity following intraperitoneal injection of amphetamine. Given orally, SR 48692 reduced dose-dependently (0.1-1 mg/kg) these intra-accumbens neurotensin effects. Using high pressure liquid chromatography with electrochemical detection, we showed that microgram amounts of neurotensin injected into the ventral tegmental area increased dihydroxyphenylacetate/dopamine ratios in the nucleus accumbens. Using in vivo voltammetry techniques, we found that the injection of nanogram and picogram amounts of neurotensin in the ventral tegmental area stimulated dopamine efflux in the nucleus accumbens. None of these biochemical changes were affected by SR 48692 (0.1-10 mg/kg). These results indicate complex interactions between neurotensin and the mesolimbic dopamine system. More particularly, the differential ability of SR 48692 to affect neurotensin-evoked behavioural versus biochemical changes supports the concept of neurotensin receptor heterogeneity.     

Implications of gastric topical bioactive peptides in ammonia-induced acute gastric mucosal lesions in rats

BACKGROUND: Ammonia, one of the pathogenic factors in Helicobacter pylori-induced mucosal injury, induces acute mucosal lesions in the rat glandular stomach. METHODS: The effect of ammonia administered intragastrically on gastric peptides was investigated in urethane-anesthetized rats. RESULTS: Gastric mucosal lesions were observed 5 min after 0.3% ammonia (4 ml/kg, intragastrically). Immunoreactive endothelin-1 (ET-1) and immunoreactive thyrotropin-releasing hormone (TRH) concentrations in the gastric wall decreased significantly 2 min and 5 min after ammonia, respectively. A significant increase in gastric juice immunoreactive ET-1 and TRH levels was reciprocally observed. The severity of gastric mucosal injury and changes in gastric immunoreactive ET-1 and TRH concentrations were shown to be concentration-dependent 30 min after ammonia. Atropine (5 mg/kg, intraperitoneally, -20 min) prevented ammonia-induced injury accompanied by a block of changes in gastric immunoreactive ET-1 and TRH concentrations. BQ-485 (ET(A) receptor antagonist; 2 mg/kg, subcutaneously) also abolished ammonia-induced lesions and gastric immunoreactive TRH changes. CONCLUSIONS: These findings suggested that gastric ET-1 and TRH play a role in ammonia-induced gastric mucosal injury mediated via a muscarine and an ET(A) receptor.     

Biphasic effects of intraaccumbens mu-opioid peptide agonist DAMGO on locomotor activities

The effects of bilateral microinjections of mu-opioid receptor agonist DAMGO (0.00, 0.01, 0.1, or 1.0 microgram/side) were tested in rats for 120 min in activity monitors. The horizontal movement, rearing, and stereotypy times in seconds were measured during 12 consecutive 10-min time blocks. DAMGO (0.01, 0.1, and 1.0 microgram) resulted in biphasic effects, inhibition followed by activation for each of the three measures. These data replicate the behavioral effects of ICV DAMGO except that the duration of the behavioral effects were longer with Acb injections.     

Enhancement of acoustic startle by electrical stimulation of the amygdala.

The present study demonstrated that electrical stimulation of the amygdala enhanced the acoustic startle response. A 25-ms train of 0.1-ms pulses initiated 5 ms before the onset of a 20-ms noise burst significantly increased startle at currents from 40 to 400 μA. Electrode placements just medial to the amygdala (in the pathway connecting the amygdala to the brain stem) increased startle with the lowest currents. Startle was also increased in all animals with stimulation in the central, medial, and intercalated nuclei of the amygdala. Stimulation in areas surrounding the amygdaloid complex was ineffective. In a second experiment, paired pulses with interpulse intervals between 0.1 and 20.0 ms delivered to the amygdala demonstrated that the stimulated axons had a distribution of refractory periods between 0.6 and 1.0 ms. This suggests that the population of neurons which subserves the enhancement of acoustic startle is fairly homogeneous and has small, myelinated axons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of nitric oxide in the nucleus of the solitary tract of rats

We have determined the role of nitric oxide (NO) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. The unilateral microinjection of Nomega-nitro-l-arginine methyl ester (10 nmol) to block the synthesis of NO into the NTS significantly decreased the arterial pressure, heart rate (HR) and renal sympathetic nerve activity (RSNA) (-19+/-2 mmHg, -23+/-5 beats/min, -30+/-2%, respectively). The microinjection of carboxy-2-phenyl-4,4,5, 5-tetramethylimidazoline-1-oxyl 3-oxide (Carboxy PTIO) (trapper of NO; 0.1 nmol) into the NTS also decreased arterial pressure and RSNA. Conversely, the microinjection of Et2N[N(O)NO]Na (NOC 18) (NO donor; 10 nmol) caused increases in arterial pressure, HR and RSNA (+14+/-2 mmHg, +11+/-2 beats/min, +38+/-7%, respectively), which was inhibited by the pre-microinjection of Carboxy PTIO (0.1 nmol). On the other hand, not only l-arginine (10 nmol) but also d-arginine (10 nmol), which is inactive to produce NO, significantly decreased the arterial pressure and RSNA. These results suggest that (1) NO acts at the NTS to increase the arterial pressure and RSNA, and (2) the microinjection of l-arginine as well as d-arginine led to decreases in arterial pressure and RSNA that were not mediated by the formation of NO in the NTS.     

The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus

We have previously shown that a membrane-permeant analog of cAMP, 8-bromo-cAMP (8-br-cAMP), elicits a vigorous eating response when microinjected into the perifornical hypothalamus (PFH) or lateral hypothalamus (LH) of satiated rats, suggesting that increases in cAMP in these areas may be important in the neural control of eating. To determine the locus of this effect, we compared the ability of 8-br-cAMP (1-100 nmol/0.3 microl) to elicit eating after microinjection into the PFH, LH, or the following bracketing areas: the anterior and posterior LH, paraventricular nucleus of the hypothalamus, thalamus, and amygdala. 8-br-cAMP at 50 nmol elicited eating (>/=3.4 gm in 2 hr) exclusively in the PFH and LH. At 100 nmol, 8-br-cAMP elicited a larger response in these areas and elicited a smaller, more variable response in the thalamus. We similarly mapped the feeding-stimulatory effects of compounds that increase endogenous cellular cAMP in naive rats. Combined microinjection of matched doses (300 nmol) of 3-isobutyl-1-methylxanthine and 7-deacetyl-7-O-(N-methylpiperazino)-gamma-butyryl-forskolin was effective exclusively in the PFH, eliciting an average 2 hr food intake of 8.4 +/- 2.0 gm. Collectively, these results suggest that increases in cellular cAMP within a specific brain site, the PFH, may play a role in the neural stimulation of eating.     

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.     

Multiple limbic regions mediate the disruption of prepulse inhibition produced in rats by the noncompetitive NMDA antagonist dizocilpine

Prepulse inhibition (PPI), a phenomenon in which a weak prestimulus decreases the startle response to an intense stimulus, provides an operational measure of sensorimotor gating (a process by which an organism filters sensory information) and is diminished in schizophrenia and schizotypal patients. The psychotomimetic phencyclidine and its potent congener dizocilpine are noncompetitive antagonists of the NMDA receptor complex, and they disrupt PPI in rodents, mimicking the clinically observed PPI deficit. The neuroanatomical substrates mediating the PPI-disruptive effects of noncompetitive NMDA antagonists are unknown. The present study sought to identify brain regions subserving the disruption of PPI produced by noncompetitive NMDA antagonists in rats. PPI was measured in startle chambers immediately after bilateral infusion of dizocilpine (0, 0.25, 1.25, and 6.25 microgram/0.5 microliter/side) into one of six brain regions: amygdala, dorsal hippocampus, medial prefrontal cortex, nucleus accumbens, ventral hippocampus, and dorsomedial thalamus. Dizocilpine significantly decreased PPI after infusion into the amygdala or dorsal hippocampus. A trend toward PPI disruption was observed with administration into medial prefrontal cortex. In contrast, no change in PPI was produced by dizocilpine infusion into nucleus accumbens, ventral hippocampus, or dorsomedial thalamus. Startle reactivity was increased by dizocilpine infusion into amygdala, dorsal hippocampus, nucleus accumbens, and dorsomedial thalamus, but not medial prefrontal cortex. These findings indicate that multiple limbic forebrain regions mediate the ability of noncompetitive NMDA antagonists to disrupt PPI and that the PPI-disruptive and the startle-increasing effects of dizocilpine are mediated by different central sites.     

Evidence for the involvement of phospholipase A2 mechanisms in the development of stimulant sensitization

Evidence suggests that phospholipase A2 (PLA2) activation is involved in numerous neuroplastic phenomena, including long-term potentiation. Considering the pharmacological similarities between long-term potentiation and stimulant sensitization, it seems possible that PLA2 inhibition activity also might have a role in the induction of stimulant sensitization. In this study, we have investigated whether PLA2 inhibition, by quinacrine, has any effects on stimulant-induced behavioral sensitization. Both locomotor and stereotypic behavioral sensitization were dose-dependently blocked in rats pretreated with quinacrine (8-25 mg/kg i.p.) 15 min before cocaine (30 mg/kg i.p.), when tested with cocaine (15 mg/kg i.p) 72 hr later. Similar results also were found with d-amphetamine (2 mg/kg i.p.) sensitization using a 10-day treatment regimen with testing on day 11. The ability of PLA2 activation, by melittin, to produce cocaine sensitization also was tested. Local injections of melittin (0.1 microgram/0.4 microliter) into the ventral tegmental area sensitized the subsequent stimulation of locomotor activity, stereotypy and nucleus accumbens dopamine release by cocaine, when tested 72 hr later. Local injections of melittin (0.1-1.0 microgram/0.8 microliter) into the nucleus accumbens had a moderate sensitizing effect on locomotion. Quinacrine (16 mg/kg) pretreatment 45 min before intraventral tegmental area melittin injection significantly decreased melittin-induced sensitization of the locomotor and stereotypy response to cocaine. These results indicate that PLA2 activation may play a role in the induction of stimulant sensitization. It is proposed that PLA2 activity in mesolimbic dopamine neurons, at the level of the cell bodies and perhaps the nerve terminals, is involved in the biochemical mechanisms mediating the development of stimulant sensitization.     

Organization of projections from the basomedial nucleus of the amygdala: a PHAL study in the rat

The organization of axonal projections from the basomedial nucleus of the amygdala (BMA) was examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The anterior and posterior parts of the BMA, recognized on cytoarchitectonic grounds, display very different projection patterns. Within the amygdala, the anterior basomedial nucleus (BMAa) heavily innervates the central, medial, and anterior cortical nuclei. In contrast, the posterior basomedial nucleus (BMAp) sends a dense projection to the lateral nucleus, and to restricted parts of the central and medial nuclei. Extra-amygdalar projections from the BMA are divided into ascending and descending components. The former end in the cerebral cortex, striatum, and septum. The BMAa mainly innervates olfactory (piriform, transitional) and insular areas, whereas the BMAp also innervates inferior temporal (perirhinal, ectorhinal) and medial prefrontal (infralimbic, prelimbic) areas and the hippocampal formation. Within the striatum, the BMAa densely innervates the striatal fundus, whereas the nucleus accumbens receives a heavy input from the BMAp. Both parts of the BMA send massive projections to distinct regions of the bed nuclei of the stria terminalis. Descending projections from the BMA end primarily in the hypothalamus. The BMAa sends a major input to the lateral hypothalamic area, whereas the BMAp innervates the ventromedial nucleus particularly heavily. Injections were also placed in the anterior cortical nucleus (COAa), a cell group superficially adjacent to the BMAa. PHAL-labeled axons from this cell group mainly ascend into the amygdala and olfactory areas, and descend into the thalamus and lateral hypothalamic area. Based on connections, the COAa and BMAa are part of the same functional system. The results suggest that cytoarchitectonically distinct anterior and posterior parts of the BMA are also hodologically distinct and form parts of distinct anatomical circuits probably involved in mediating different behaviors (for example, feeding and social behaviors vs. emotion-related learning, respectively).