ABSTRACT
An overlapping distribution of alpha2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and alpha2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of alpha2-adrenergic receptors of the dorsal hippocampus on WIN55.212-2 state-dependent learning. Adult male Wistar rats were bilaterally implanted with chronic cannulae in the CA1 regions of their dorsal hippocampi trained in a step-down type inhibitory avoidance task and tested 24 hr after training, to measure step-down latency. Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 [0.25 and 0.5microg/rat] induced amnesia. Amnesia produced by post-training WIN55,212-2 [0.5 microg/rat] was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microinjections of clonidine [0.25, 0.5 and 1 microg/rat] or yohimbine [0.5, 0.75, and 1 MQ/rat] did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine [0.5 and 1 micro9/rat] or clonidine [0.25, 0.5, and 1 microg/rat] with an ineffective dose of WIN 55,212-2 [0.25 microg/rat] reversed post-training WIN55,212-2 [0.5 microg/rat,intra-CA1] induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine [1 microg/rat] before administration of WIN55,212-2 [0.5 microg/rat, intra-CA1], however, dose-dependently inhibited WIN55.212-2 state-dependent memory. Modulation of a2-adrenergic receptors in the dorsal hippocampal CA1 regions can influence WIN55, 212-2 induced amnesia and WIN55,212-2 state-dependent learning of an inhibitory avoidance task by pre- or post-synaptic mechanism[s]
Subject(s)
Animals, Laboratory , Male , Adrenergic alpha-2 Receptor Agonists/pharmacology , Adrenergic alpha-2 Receptor Antagonists/pharmacology , Behavior, Animal/drug effects , Benzoxazines/pharmacology , CA1 Region, Hippocampal/physiology , Cannabinoid Receptor Antagonists , Clonidine/pharmacology , Memory/drug effects , Rats, Wistar , Statistics, NonparametricABSTRACT
The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (< 24 h), the juvenile (28-30 days) and the adult groups (90 - 100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively, for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats, and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P < 0.01). The cholesterol content was 2.92 +/- 0.03 mg/g, 11.20 +/- 3.41 mg/g and 12.91 +/- 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P < 0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.