Seven daily social defeat sessions increased water (but not food) intake, sucrose preference, anxiety, cued fear expression, and adrenal weight in C57BL/6N mice. The first and the last social stress sessions triggered immediate brain region-dependent changes in the concentrations of the principal endocannabinoids anandamide and 2-arachidonoylglycerol. Pretreatment before each of the seven stress sessions with the CB1 receptor Selleckchem S63845 antagonist rimonabant prolonged freezing responses of stressed mice during cued fear recall tests. Repeated social stress abolished the increased fear expression displayed by constitutive CB1 receptor-deficient mice. The use of mutant mice lacking CB1 receptors

from cortical glutamatergic neurons or from GABAergic neurons indicated that it is the absence of the former CB1 receptor

population that is responsible for the fear responses in socially stressed CB1 mutant mice. In addition, stress-induced hypolocomotor reactivity was amplified by the absence of CB1 receptors from GABAergic neurons. Mutant mice lacking CB1 receptors from serotonergic neurons displayed a higher anxiety but decreased cued fear expression than Selleckchem Acalabrutinib their wild-type controls. These mutant mice failed to show social stress-elicited increased sucrose preference. This study shows that (i) release of endocannabinoids during stress exposure impedes stress-elicited amplification of cued fear behavior, (ii) social stress opposes the increased fear expression and delayed between-session extinction because of the absence of CB1 receptors from cortical glutamatergic

neurons, and (iii) CB1 receptors on central serotonergic neurons are involved in the sweet consumption response to repeated stress. Neuropsychopharmacology (2012) 37, 1885-1900; doi:10.1038/npp.2012.36; published online 21 March 2012″
“Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement.

To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning.

Nicotine improved learning and increased find more brain levels of dihydroxyphenylacetic acid (DOPAC), the primary dopamine metabolite. There was a significant correlation between choice accuracy and DOPAC levels. The nicotinic antagonist mecamylamine blocked the nicotine-induced increase in DOPAC concentrations, in line with our previous finding that mecamylamine reversed nicotine-induced learning improvement.

Dopamine systems are related to learning in zebrafish; nicotine exposure increases both learning rates and DOPAC levels; and nicotinic antagonist administration blocks nicotine-induced rises in DOPAC concentrations.