Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats

The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03–0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V1a receptors. Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V1a receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1 mg/kg, which did not alter activity and had little effect on temperature, significantly attenuated phencyclidine-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex, without influencing serotonin efflux. Systemic oxytocin administration attenuated phencyclidine-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced nucleus accumbens dopamine release, consistent with activation of mesocorticolimbic circuits regulating associative/reward behavior being involved. This highlights the therapeutic potential of oxytocin to treat social behavioral deficits seen in psychiatric disorders such as schizophrenia

Electrical conduction by interface states in semiconductor heterojunctions

peer reviewedaudience: researcher, professionalElectrical conduction in semiconductor heterojunctions containing defect states in the interface region is studied. As the classical drift-diffusion mechanism cannot in any case explain electrical conduction in semiconductor heterojunctions, tunnelling involving interface states is often considered as a possible conduction path. A theoretical treatment is made where defect states in the interface region with a continuous energy distribution are included. Electrical conduction through this defect band then allows the transit of electrons from the conduction band of one semiconductor to the valence band of the second component. The analysis is initiated by electrical measurements on n-CdS/p-CdTe heterojunctions obtained by chemical vapour deposition of CdS on (111) oriented CdTe single crystals, for which current--voltage and capacitance--frequency results are shown. The theoretical analysis is based on the numerical resolution of Poisson's equation and the continuity equations of electrons, holes and defect states, where a current component corresponding to the defect band conduction is explicitly included. Comparison with the experimental curves shows that this formalism yields an efficient tool to model the conduction process through the interface region. It also allows us to determine critical values of the physical parameters when a particular step in the conduction mechanism becomes dominant

Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Psychopharmacology 213

Abstract Rationale 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an acute release of 5-HT in the brain, together with increased locomotion and hyperthermia. Objective This study examined whether the acute functional changes of locomotor activity and body temperature are related to enhanced 5-HT release induced by MDMA. Methods We concomitantly measured changes in extraneuronal 5-HT by in vivo brain microdialysis and used radiotelemetry to measure locomotion and body temperature to establish whether any positive correlations occur between these three parameters. 'Binge-type' repeated administration of low doses of MDMA (3 and 6 mg/kg given at 2-h intervals three times) were given to provide drug exposure similar to that experienced by recreational drug users. Results MDMA induced acute hyperactivity, changes in core body temperature (both hypothermia and hyperthermia) and elevation of hippocampal 5-HT overflow, all of which were dependent on the dose of MDMA administered. The change in locomotor activity and the magnitude of the hyperthermia appeared to be unrelated both to each other and to the magnitude of MDMA-induced 5-HT release. The study also found evidence of long-term disruption of novel object discrimination 2 weeks following "binge-type" repeated MDMA administration. Conclusions MDMA-induced 5-HT release in the brain was not responsible for either the hyperthermia or increased locomotor activity that occurred. Since neither dose schedule of MDMA induced a neurotoxic loss of brain 5-HT 2 weeks after its administration, the impairment of recognition memory found in novel object discrimination probably results from other long-term changes yet to be established

Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota immune-brain axis

Early-life stress is an established risk for the development of psychiatric disorders. Post-weaning isolation rearing of rats produces lasting developmental changes in behavior and brain function that may have translational pathophysiological relevance to alterations seen in schizophrenia, but the underlying mechanisms are unclear. Accumulating evidence supports the premise that gut microbiota influence brain development and function by affecting inflammatory mediators, the hypothalamic-pituitaryadrenal axis and neurotransmission, but there is little knowledge of whether the microbiota-gut-brain axis might contribute to the development of schizophrenia-related behaviors. To this end the effects of social isolation (SI; a well-validated animal model for schizophrenia)-induced changes in rat behavior were correlated with alterations in gut microbiota, hippocampal neurogenesis and brain cytokine levels. Twenty-four male Lister hooded rats were housed in social groups (group-housed, GH, 3 littermates per cage) or alone (SI) from weaning (post-natal day 24) for four weeks before recording open field exploration, locomotor activity/novel object discrimination (NOD), elevated plus maze, conditioned freezing response (CFR) and restraint stress at one week intervals. Post-mortem caecal microbiota composition, cortical and hippocampal cytokines and neurogenesis were correlated to indices of behavioral changes. SI rats were hyperactive in the open field and locomotor activity chambers traveling further than GH controls in the less aversive peripheral zone. While SI rats showed few alterations in plus maze or NOD they froze for significantly less time than GH following conditioning in the CFR paradigm, consistent with impaired associative learning and memory. SI rats had significantly fewer BrdU/NeuN positive cells in the dentate gyrus than GH controls. SI rats had altered microbiota composition with increases in Actinobacteria and decreases in the class Clostridia compared to GH controls. Differences were also noted at genus level. Positive correlations were seen between microbiota, hippocampal IL-6 and IL-10, conditioned freezing and open field exploration. Adverse early-life stress resulting from continuous SI increased several indices of 'anxiety-like' behavior and impaired associative learning and memory accompanied by changes to gut microbiota, reduced hippocampal IL-6, IL-10 and neurogenesis. This study suggests that early-life stress may produce long-lasting changes in gut microbiota contributing to development of abnormal neuronal and endocrine function and behavior which could play a pivotal role in the aetiology of psychiatric illness

Investigation of stretching behaviour induced by the selective 5-HT(6) receptor antagonist, Ro 04-6790, in rats

1. The present study examined the effects of the selective 5-HT(6) receptor antagonist 4-amino-N-(2, 6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) on locomotor activity and unconditioned behaviour in male Sprague Dawley rats (230–300 g). 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(−1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing. The latter behaviour was most pronounced between 30 and 90 min following the administration of Ro 04-6790. 3. Detailed analysis of the stretching and yawning behaviour showed that Ro 04-6790 (3, 10 or 30 mg kg(−1), i.p.) dose-dependently induced stretching. The number of stretches observed following treatment with either Ro 04-6790 (10 mg kg(−1) i.p.) or Ro-04-6790 (30 mg kg(−1), i.p.) was significantly greater than that observed in saline-treated rats. The yawning behaviour, however, was not dose-dependent nor was the number of yawns in any of the drug treated groups significantly greater than in those treated with saline. 4. Pretreatment (30 min) with the non-selective muscarinic antagonists scopolamine (0.1, 0.3 or 1 mg kg(−1), i.p.) and atropine (0.3, 1 or 3 mg kg(−1), s.c.) but not methylatropine (1, 3 or 10 mg kg(−1), s.c) significantly inhibited stretching induced by Ro 04-6790 (30 mg kg(−1), i.p.). 5. The dopamine D(2)-like receptor antagonist, haloperidol (0.03, 0.1 or 0.3 mg kg(−1), s.c.) given at the same time as Ro 04-6790 (30 mg kg(−1), i.p.) had no effect on the stretching induced by the 5-HT(6) antagonist. 6. These data suggest that systemic injection of the 5-HT(6) antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT(6) receptor blockade. There is no evidence for dopamine D(2)-like receptor involvement in this behaviour