GABA_b Receptor Antagonist (CGP₃₅₃₄₈) Improves Testosterone Induced Spatial Acquisition Impairment in Adult Male Rat

Abstract

The high density of the androgen receptors in fundamental centers of learning and memory, such as hippocampus, shows that there must be some relationship between the androgen receptors and cognitive aspects. On the other hand, Gama Amino Butric Acid (GABA) plays a controlling role in the balance of excitability and inhibitory states in the cortex and hippocampus; a number of reports suggest that removal of the influence of inhibitory GABA receptors lead to memory enhancement and conversely the activation lead to memory inhibition. Sex steroids can rapidly influence neural activity by increasing the binding affinity of neurotransmitters such as GABAergic. To determine the effect of Testosterone on learning and memory in CA 1 region of hippocampus, male albino Wistar rats (200 - 250 g) are bilaterally cannulated into CA 1 of hippocampus then different doses of Testosterone enanthate or CGP 35348 are injected through the cannulae for assessing of acquisition, consolidation and retrieval in a single-day testing protocol of Morris water maze task. After hippocampal microinjection with Testosterone (T), acquisition is significantly impaired, while after treatment with CGP 35348 , acquisition impairment caused by T can be significantly improved. Also T and CGP 35348 have no significant effect on consolidation and retrieval stages of spatial memory. These results suggest that CGP 35348 may have therapeutic value in the treatment of Testosterone-induced acquisition impairment.