Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deficits in discriminated learning remain despite clearance of long-term persistent viral infection in mice

Mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit impaired learning ability. In this report, we determined whether clearance of the virus was associated with restoration of behavioral function. Neonatal Balb/cByJ mice were persistently infected with LCMV and tested as adults in a nonconditional spatial discrimination task. The presence of viral proteins in neurons was confirmed immunohistochemically and infectious virus was quantified in the blood by plaque assay. LCMV-infected adult mice made more errors in a Y-maze avoidance task compared to sham-inoculated controls. After the initial behavioral analysis, infected and control mice received a dose of cytotoxic T-lymphocytes sufficient to clear virus from these mice. Following complete clearance of the virus, mice were re-tested in the behavioral task, 5 months after the original test. No reversal of the learning deficit was seen following viral clearance; mice that had been cleared of the virus and those that remained persistently infected behaved similarly. These data indicate that persistent LCMV infection of the CNS lasting up to 7 months results in discriminated learning impairments that are not reversed by subsequent anti-viral immunocytotherapy.     

Syntheses of new black dyes for ink-jet inks

Drop-on-demand ink-jet inks made from dyes generally show poor light and wet fastness. A number of studies have been carried out previously to improve the fastness of such inks by introducing novel dyes and new additives. Based on the research results, use of fast dyes could give ink-jet inks with good properties. This study describes new black dyes for aqueous ink-jet inks, which show better light and wet fastness and print quality, compared to an analogous ink formulated from CI Food Black 2.     

Estrous cycle effects on operant responding for ethanol in female rats

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self-administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self-administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4-day estrous cycle, whereas free-running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.     

Design of a 3-D fully depleted SOI computational RAM

We introduce a three-dimensional (3-D) processor-in-memory integrated circuit design that provides progressively increasing processing power as the number of stacked dies increases, while incurring no extra design effort or mask sets. Innovative techniques for processor/memory redundancy and fast global bus evaluation are described. The architecture can be augmented with a nearest-neighbor physical 3-D communications network that can substantially reduce interconnect lengths and relieve routing congestion. The test chip, with 128 Kb of memory and 512 processing elements (PEs) on two fully depleted silicon-on-insulator (SOI) dies, can achieve a peak of 170 billion-bit-operations per second at 400 MHz.     

Clonidine blocks acquisition but not expression of conditioned opiate withdrawal in rats

Previous studies in rodents have reported that clonidine, an alpha 2-adrenergic receptor agonist, attenuated conditioned aversions to naloxone-precipitated opiate withdrawal when administered prior to each withdrawal conditioning episode. The current study was designed to determine whether clonidine could modify the expression of previously established conditioned place aversions and conditioned suppression of operant responding. Dose- and time-dependent effects of clonidine on activity and suppression of operant responding for food identified appropriate treatment parameters for subsequent studies in which rats rendered dependent on opiates through implantation of morphine pellets were tested for: (1) conditioned place aversion; and (2) conditioned suppression of operant responding for food (fixed ratio-15 schedule), in a paradigm wherein rats received four pairings of naloxone with a distinct tone and odor stimulus. Clonidine dose-dependently blocked the acquisition of both conditioned behaviors when administered prior to naloxone on each conditioning trial, but was ineffective in blocking the expression of these conditioned withdrawal signs when administered prior to the test session.     

CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats

Recent reports have provided evidence of a link between the endogenous brain cannabinoid system and the endogenous central opioid systems. Here we report that the selective CB1 receptor antagonist SR 141716A induced behavioral and endocrine alterations associated with opiate withdrawal in morphine-dependent animals in a dose-dependent manner and that naloxone induced an opiate withdrawal syndrome in animals made cannabinoid-dependent by repeated administration of the potent cannabinoid agonist HU-210. Additionally CB1 and mu-opioid receptor mRNAs were co-localized in brain areas relevant for opiate withdrawal such as the nucleus accumbens, septum, dorsal striatum, the central amygdaloid nucleus and the habenular complex. These results suggest that CB1 cannabinoid receptors may play a role in the neuroadaptive processes associated with opiate dependence, and they lend further support for the hypothesis of a potential role of cannabinoid receptors in the neurobiological changes that culminate in drug addiction.     

Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol

Ventilatory acclimatization to sustained hypoxia (VASH) is the time-dependent increase in ventilation that occurs during prolonged exposure to hypoxia. We tested the hypothesis that carotid body (CB) dopaminergic mechanisms are down-regulated during VASH, which would allow CB afferent discharge and ventilation to increase beyond the initial response to hypoxia. Domperidone (DOM; 1.0 mg.kg-1) was administered intravenously to block CB dopamine (DA) receptors after VASH was complete in awake goats. DOM caused a significant augmentation of the ventilatory response to hypoxia in acclimatized goats, failing to support the hypothesis. We conclude that inhibitory CB dopaminergic function is not significantly reduced following prolonged hypoxia, and that down-regulation of CB dopaminergic mechanisms may not be involved in VASH in the goat.     

Differences in the liability to self-administer intravenous cocaine between C57BL/6 x SJL and BALB/cByJ mice

Application of animal models of psychostimulant abuse for experimentation in mice is becoming increasingly important for studying the contribution of genetic differences, as well as the roles of selected (targeted) genes, in specific behaviors. The purpose of this study was to investigate strain differences in cocaine self-administration behavior between C57BL/6 x SJL hybrid mice and BALB/cByJ mice. These two strains were chosen because BALB/cByJ mice have a well-developed behavioral pharmacological profile, and hybrid strains on a C57BL/6 background are commonly used for generating transgenic expressing and knockout mutant mice. C57BL/6 x SJL mice dose-dependently acquired cocaine self-administration (1.0 mg/kg/injection but not 0.25 mg/kg/injection) by responding selectively in the active nose-poke hole and maintaining stable levels of daily drug intake; they also exhibited a characteristic inverted-U-shaped cocaine dose-effect function. BALB/cByJ mice failed to acquire cocaine self-administration at either dose under the same test conditions. The strain differences observed in self-administration did not seem to be attributed to other behavioral differences because the two strains exhibited similar amounts of spontaneous nose-poking in the absence of reinforcers, and BALB/cByJ mice responded more than C57BL/6 x SJL mice in a food-reinforced nose-poke operant task. Importantly, the dose-effect function for the motor stimulating effects of cocaine (3.8-30 mg/kg intraperitoneally) suggests enhanced sensitivity but reduced efficacy of cocaine in stimulating motor activity in BALB/cByJ mice relative to the C57BL/6 x SJL hybrid mice. These results indicate that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is not the result of differences in spontaneous activity or performance, but may reflect different sensitivities to the reinforcing, or rate-disrupting, properties of cocaine. The data support an influence of genetic background in the liability to self-administer cocaine. Thus, a hypothesis is proposed that the decreased liability of BALB/cByJ mice to acquire cocaine self-administration is related to differences in brain monoamine systems linked to the high "emotionality" profile of BALB/c mice in novel or fearful situations, including perhaps cocaine administration.     

Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat

The effect of a dopamine receptor antagonist on locomotor activity was examined during withdrawal from either self-administered or experimenter-administered cocaine. In the self-administration experiment, the locomotor response to a challenge injection of cis-flupenthixol was assessed in photocell cages at 4 h after the cessation of a 12-h cocaine self-administration session. Rats which had self-administered cocaine, and were challenged with cis-flupenthixol (0.05 mg/kg), were found to be hypoactive relative to controls. In the experimenter-administered cocaine experiment, animals were given eight IP injections of 15 mg/kg cocaine over a 9.5-h period, for a total of 120 mg/kg. At 4, 8, and 24 h (tested in three separate groups of rats) after cessation of the eight injections, the locomotor response to a challenge injection of saline or cis-flupenthixol was tested. Cocaine-treated animals displayed a dose-dependent, heightened sensitivity to the locomotor depressant effects of 0.05 mg/kg and 0.2 mg/kg cis-flupenthixol 4 h post-cocaine, whereas they did not show increased sensitivity to 0.05 mg/kg cis-flupenthixol 8 or 24 h post-cocaine. However, cocaine-treated animals displayed a mild hypoactivity 8 h post-cocaine. In a separate group of animals, a dose-response experiment was performed which indicated that a dose of cis-flupenthixol as high as 0.2 mg/kg was required to produce locomotor depression in cocaine-naive rats. The results of this study support clinical observations of dopamine antagonist-precipitated motor dysfunction in abstinent cocaine abusers, and lend further support to the hypothesis that alterations in dopaminergic neurotransmission consequent to prolonged cocaine exposure are partly responsible for some of the symptoms of cocaine withdrawal.