Behavioral changes and dendritic remodeling of hippocampal neurons in adolescent alcohol-treated rats

Objective: Earlier, we and others have reported that alcohol exposure in adolescent rat impaired performance of a spatial memory task in the Morris water maze. The goal of the present study was to investigate the effects of acute adolescent alcohol treatment on the hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear) memories. The study also looked at the structural changes in anterior CA1 hippocampal neurons in adolescent alcohol-treated rats.Methods: Adolescent female rats were administered with a single dose of alcohol (1.0, 1.5, or 2.0 g/kg) or vehicle either before training (pre-training) or after training (pre-testing). Experimental and control rats were trained in the fear conditioning paradigm, and 24 h later tested for both contextual fear conditioning as well as cued fear memory. Separate groups of rats were treated with either alcohol (2 g/kg) or vehicle and sacrificed 24 h later. Their brains were harvested and processed for rapid Golgi staining. Randomly selected CA1 pyramidal neurons were analyzed for dendritic branching and dendritic spine density.Results: Pre-training alcohol dose-dependently attenuated acquisition of hippocampus-dependent contextual fear conditioning but had no effect on the acquisition of amygdala-associated cued fear. When administered following training (pre-testing), alcohol did not alter either contextual conditioning or cued fear memory. Golgi stained CA1 pyramidal neurons in alcohol treated female rats had reduced basilar tree branching and less complex dendritic arborization.Conclusion: Alcohol specifically impaired hippocampal learning in adolescent rats but not amygdala-associated cued fear memory. Compared to vehicle-treated rats, CA1 hippocampal pyramidal neurons in alcohol-treated rats had less complex dendritic morphology. Together, these data suggest that adolescent alcohol exposure produces changes in the neuronal organization of the hippocampus, and these changes may be related to impairments in hippocampus-dependent memory formation

Antagonists of N-methyl-d-aspartate receptor partially prevent the development of cocaine sensitization

Behavioral sensitization to cocaine was tested for in rats pretreated with MK-801, a noncompetitive ^À/-methyl-D-aspartate (NMDA) receptor antagonist, or D-3-(2-carborypiperaan-4-yl)-l-propenyl-l-phosphonic acid (D-CPPene), a competitive NMDA antagonist. A 5-day regimen of once-daily ssç¡ine (15 mglkg) injections yielded sensitization to cocaine (15 mglkg)-induced behavioral activation. Cocaine sensitiz¿tion lilas partially prevented by MK-801 (0.25 m/kg) or D-CPPene (2A mdks) pretreatment. These rezults differ from previous reports that NMDA receptor antagonists completely prevented tåe development of stimulant sensitization. While raising questions about methodological differences among laboratories studying this iszue, our findings suggest that sensitization may involve mechanisms dependent on NMDA-receptor function as well as NMDA receptor-independent mechanisms

Centchroman: in vitro metabolism by rat liver homogenate

Centchroman (trans-2,2-dimethyl-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman) (I), a postcoital antifertility agent under clinical development was extensively metabolized by rat liver homogenate in vitro. Employing field desorption mass spectrometry, high performance liquid chromatography, comparison with authentic samples, and studies with 2-14C-Centchroman, seven metabolites have so far been characterised, which include trans-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman (II, 37.5%), trans-2,2-dimethyl-3-phenyl-4-(p-(β pyrrolidinoethoxy) phenyl)-7-hydroxy chroman (III, 2.5%), β pyrrolidino-ethoxy benzene (IV), 2,2-dimethyl-4-(p-(hydroxy) phenyl)-7-methoxy chromene (V, 39.4%), trans-2,2-dimethyl-3-phenyl-4-(p-(hydroxy) phenyl)-7-methoxy chroman (VI, 5.8%), 2,3-trans-3,4-trans-2-methyl-3-phenyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chorman (VII, 2.9%), and 2,2-dimethyl-4-(p-(β-pyrrolidinoethoxy) phenyl)-7-methoxy chroman (VIII, 8.8%). Formation of metabolites V and VIII are unusual cases of dephenylation during metabolism