Koenigbroch6330

The regulation of the glutamatergic and dopaminergic neurocircuitry by clock genes is postulated to be the main circadian mechanism underlying the escalation of drug addiction. The bidirectional interaction between the circadian system and drug addiction seems to be mediated by the effects caused by each drug or class of drugs of abuse. These studies provide new insights on the development of successful strategies aimed at restoring/stabilizing circadian rhythms to reduce the risk for addiction development and relapse.Neurodevelopmental abnormalities are associated with cognitive dysfunction in schizophrenia. In particular, deficits of working memory, are consistently observed in schizophrenia, reflecting prefrontal cortex (PFc) dysfunction. To elucidate the mechanism of such deficits in working memory, the pathophysiological properties of PFc neurons and synaptic transmission have been studied in several developmental models of schizophrenia. Given the pathogenetic heterogeneity of schizophrenia, comparison of PFc synaptic transmission between models of prenatal and postnatal defect would promote our understanding on the developmental components of the biological vulnerability to schizophrenia. In the present study, we investigated the excitatory synaptic transmission onto pyramidal cells localized in layer 5 of the medial PFc (mPFc) in two developmental models of schizophrenia gestational methylazoxymethanol acetate (MAM) administration and post-weaning social isolation (SI). We found that both models exhibited defective spatial working memory, as indicated by lower spontaneous alternations in a Y-maze paradigm. The recordings from pyramidal neurons in both models exhibited decreased spontaneous excitatory postsynaptic current (sEPSC), representing the reduction of excitatory synaptic transmission in the mPFc. Interestingly, a positive correlation between the impaired spontaneous alternation behavior and the decreased excitatory synaptic transmission of pyramidal neurons was found in both models. These findings suggest that diminished excitatory neurotransmission in the mPFc could be a common pathophysiology regardless of the prenatal and postnatal pathogenesis in developmental models of schizophrenia, and that it might underlie the mechanism of defective working memory in those models.Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice. The animals were rendered dependent on morphine by i.p. injection of increasing doses of morphine (10-60 mg/kg). The negative state associated with naloxone (1 mg/kg s.c.) precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. B6 mice obtained a higher aversion score and took longer to extinguish the aversive memory than Swiss mice. In addition, corticosterone levels were increased after CPA expression. Moreover, corticosterone levels were decreased during CPA extinction in Swiss mice without changes in B6 mice. Pre-treatment with the selective CRF1 receptor antagonist CP-154,526 before naloxone, impaired morphine-withdrawal aversive memory acquisition and decreased the extinction period. CP-154,526 also antagonized the increased levels of corticosterone observed after CPA expression in Swiss mice, without any changes in B6 mice. These results indicate that HPA axis could be a critical factor governing opioid withdrawal memory storage and retrieval, but in a strain or stock-specific manner. The differences observed between Swiss and B6 mice suggest that the treatment of addictive disorders should consider different individual predisposition to associate the aversive learning with the context.Cannabis use has been increasing in recent years, particularly among women, and one of the most common uses of cannabis for medical purposes is pain relief. Pain conditions and response to analgesics have been demonstrated to be influenced by sex, and evidence is emerging that this is also true with cannabinoid-mediated analgesia. In this review we evaluate the preclinical evidence supporting sex differences in cannabinoid pharmacology, as well as emerging evidence from human studies, both clinical and observational. Numerous animal studies have reported sex differences in the antinociceptive response to natural and synthetic cannabinoids that may correlate to sex differences in expression, and function, of endocannabinoid system components. Female rodents have generally been found to be more sensitive to the effects of Δ9-THC. This finding is likely a function of both pharmacokinetic and pharmacodynamics factors including differences in metabolism, differences in cannabinoid receptor expression, and influence of ovarian hormones including estradiol and progesterone. Preclinical evidence supporting direct interactions between sex hormones and the endocannabinoid system may translate to sex differences in response to cannabis and cannabinoid use in men and women. Further research into the role of sex in endocannabinoid system function is critical as we gain a deeper understanding of the impact of the endocannabinoid system in various disease states, including chronic pain.To understand the correlation between animal behaviors and the underlying neuronal circuits, it is important to monitor and record neurotransmission in the brain of freely moving animals. RGDyK chemical structure With the development of fiber photometry, based on genetically encoded biosensors, and novel electrochemical biosensors, it is possible to measure some key neuronal transmission events specific to cell types or neurotransmitters of interest with high temporospatial resolution. This review discusses the recent advances and achievements of these two techniques in the study of neurotransmission in animal models and how they can be used to complement other techniques in the neuroscientist's toolbox.