A simple, sensitive and reliable assay for serotonin and 5-HIAA in brain tissue using liquid chromatography with electrochemical detection

An extremely sensitive and simple method for simultaneously measuring both serotonin and 5-hydroxyindoleacetic acid (5-HIAA) has been developed using liquid chromatography (LC) and electrochemical detection. Assay conditions are described which resolve and measure as little as 22 picograms of serotonin and its deaminated metabolite in deproteinated brain samples.     

Increased Neostriatal Tyrosine Hydroxylation During Stress: Role of Extracellular Dopamine and Excitatory Amino Acids

Abstract: We examined the regulation of neostriatal tyrosine hydroxylation during acute stress, testing the hypothesis that excitatory amino acids (EAAs) contribute to the stress-evoked increase in dopamine (DA) synthesis. Dialysis probes implanted into neostriatum permitted delivery of drugs and sampling of extracellular fluid. Rats were exposed to 30 min of intermittent tail shock during infusion of an inhibitor of aromatic amino acid decarboxylase (AAAD), NSD-1015 (100 µM), and DOPA was measured in the dialysate. Tail shock was applied beginning either 15 min after the onset of NSD-1015 treatment (the initial rate of DOPA accumulation) or 75 min after the onset of treatment (when DOPA had approached steady state). Tail shock increased the steady-state levels of extracellular DOPA in neostriatum (+40%). However, there was no change in the initial rate of DOPA accumulation unless animals also received the D₂ receptor antagonist eticlopride (50 nM), in which case an increase was observed (+228%). The impact of tail shock on the steady-state level of DOPA was attenuated by the D₂ agonist quinpirole (100 µM), or by 2-amino-5-phosphonovalerate (APV) (100 µM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (100 µM), EAA antagonists acting at NMDA or d ,l -α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, respectively. These data suggest that acute stress normally has little effect on tyrosine hydroxylation in neostriatum due to the inhibitory influence of DA in the extracellular fluid. However, when that influence is absent (e.g., during extended inhibition of DOPA decarboxylation or blockade of DA receptors), stress increases tyrosine hydroxylation via EAAs acting on NMDA and AMPA receptors. Thus, EAAs released from corticostriatal projections may stimulate DA synthesis and thereby restore dopaminergic activity under conditions in which the availability of DA for release has been compromised.     

Migration and mutation in stochastic models of gene frequency change

Summary Migration has in the past been introduced deterministically into stochastic gene frequency models. Migration at rate m then reduces the between-population variability by a factor of (1 – m)² each generation. We show that with stochastic migration, whether of fixed or variable numbers of individuals, a positive term _m is added to the variance. As a result of the _m term, the equilibrium value of the between-population variability is increased compared to the corresponding value for deterministic migration by a factor of approximately (1 – m)^–2 for small m. An equivalent result is derived for mutation, using the infinite allele model for a single population. We show in addition that these results may be derived much more simply by use of identity-by-descent probability methods, but only if a modified definition of the probability of identity-by-descent is used, involving the sampling with instead of without replacement of pairs of genes from the population.     

A two-sex polygenic model for the evolution of premating isolation. I. Deterministic theory for natural populations

It is proposed that mating behavior is normally determined by independent genetic systems in the male and female. A specific model is put forward in which mating behavior is determined by additive gene contributions in both sexes, and the strength of mating attraction is maximized when mating "scores" in the two sexes are equalized. This type of model, which may be described as a "facilitation" model, is related to models proposed by a number of authors. It is pointed out that a second class of models exists, "avoidance" models, and that these, although less tractable analytically, could be more realistic.-An organism is assumed to be divided into two strains, and selection is introduced through lethality or sterility of the hybrid (postmating isolation). The selective tendency for divergence of mating behavior in one sex is then shown to be proportional to the amount of divergence that already exists in the opposite sex, multiplied by a quantity that can be described as the heritability of mating attraction. The situation in which no initial divergence exists in either sex constitutes an equilibrium that is unstable, but one that requires substantial deviations before any selective progress can be made. Thus, the evolution of premating isolation to reinforce postmating isolation may be an inefficient process. The process would occur much more efficiently if some initial chance divergence in mating behavior occurred during the period in which postmating isolation evolved.     

Pharmacological profile of depressor response elicited by sarthran in rat ventrolateral medulla

Injection of sarthran, an angiotensin receptor antagonist, bilaterally into the rostral ventrolateral medulla (RVLM) of alpha-chloralose-anesthetized rats decreases arterial pressure (AP) to the same extent as total autonomic blockade. This response is not reproduced by selective AT(1) antagonists. To examine the pharmacological profile of the response elicited by [Sar(1), Thr(8)]ANG II (sarthran), the ability of angiotensin analogs to inhibit the effect of sarthran injected into the RVLM was tested. Coinjection of angiotensin II (ANG II) prevented the sarthran-evoked decrease in AP, but this action of ANG II was markedly attenuated by pretreatment of the RVLM with the aminopeptidase inhibitor amastatin. Coinjection of ANG(3-8) or a selective agonist of AT(4) receptors prevented the effect of sarthran injected into the RVLM. ANG(1-7) was also able to prevent the effect of sarthran. None of the angiotensin fragments tested substantially altered blood pressure when injected alone into the RVLM. These results suggest that the depressor action of sarthran injected into the RVLM is not dependent on ANG II receptors, though the nature of the site or sites of action of sarthran within the RVLM remains uncertain.     

Water ingestion provides an early signal inhibiting osmotically stimulated vasopressin secretion in rats

Dehydrated dogs are known to inhibit secretion of vasopressin (VP) within minutes after drinking water, before plasma osmolality (P(osmol)) diminishes. The present studies determined whether water ingestion causes a similar rapid inhibition of neurohypophyseal hormone secretion in rats. Adult rats were infused with 1 M NaCl (2 ml/h iv) for 240 min to stimulate VP and oxytocin (OT) secretion. After 220 min of infusion, rats were given water to drink for 5 min, and blood samples were taken 5 and 15 min later for RIA. Plasma VP (pVP) was much lower when rats ingested water than when they drank nothing even though P(osmol) was not significantly altered. Plasma OT (pOT) was affected similarly. In contrast, no effects on pVP or pOT occurred when rats drank isotonic NaCl solution for 5 min in amounts comparable to the water intakes (approximately 5.5 ml). These results suggest that neurohypophyseal secretion of VP and OT in rats is inhibited rapidly by water drinking, and that this inhibition is mediated by a visceral signal of osmotic dilution rather than by the act of drinking per se.     

Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats

Previous experiments have indicated that arterial hypotension increases plasma oxytocin (OT) levels in rats and that OT infused intravenously causes an increase in plasma renin activity (PRA). The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats. In conscious male rats, intravenous injection of hydralazine or diazoxide produced sustained hypotension and evoked a significant increase in PRA, as expected. Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats.     

Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats

The present study sought to determine whether increases in arterial blood pressure inhibited drinking behavior evoked by ANG II, hyperosmolality, or hypovolemia in rats. Cumulative water intakes in 60- or 90-min tests and latency to the first lick were recorded as indexes of thirst. During intravenous infusions of 100 ng. kg(-1). min(-1) ANG II, attenuation of the induced increases in arterial pressure with the arteriolar vasodilator diazoxide resulted in greater water intakes and shorter latencies to drink. Drinking behavior stimulated by intravenous infusion of hypertonic saline was significantly inhibited by increases in arterial pressure caused by intravenous infusion of phenylephrine or endothelin-1, and this inhibition of drinking was proportional to the induced increase in pressure. Upon termination of the phenylephrine infusion, mean arterial pressure returned to basal values, and drinking was restored. Phenylephrine-induced increases in arterial pressure also inhibited drinking behavior in response to hypovolemia that could not be explained by differences in plasma renin activity, plasma protein concentration, or plasma osmolality. Thus increases in arterial pressure inhibit water drinking behavior in response to each of these three thirst stimuli in rats.