ACTION OF DELTA-9-TETRAHYDROCANNABINOL ON GABA(A) RECEPTOR-MEDIATED RESPONSES IN A GREASE-GAP RECORDING PREPARATION OF THE RAT HIPPOCAMPAL SLICE

We have investigated the effects of Delta-9-tetrahydrocannabinol (Delt a-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, a nd the selective GABAA receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 mu M, respectively. Resp onses to both of these agonists were selectively reduced by the noncom petitive GABAA antagonist picrotoxin (5 mu M), but were unaffected by the GABAB antagonist 2-hydroxy-saclofen (500 mu M). Responses evoked b y the selective GABAB receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 mu M) , potentiated responses to GABA, but not to muscimol. Similarly, 10-10 00 nM Delta-9-THC had no significant effect on the response to muscimo l, whereas 1000 nM Delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but musci mol is not, the results are consistent with the suggestion that Delta- 9-THC inhibits the uptake of GABA in the hippocampus. (C) 1997 Elsevie r Science Ltd.