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 (delta-9-THC) on gamma-aminobutyric acid (GABA) receptor-mediated responses in a grease-gap recording preparation of the rat hippocampus. GABA, and the selective GABA(A) receptor agonist muscimol, evoked depolarizing responses with EC50 values of 8.5 mM and 17.0 microM, respectively. Responses to both of these agonists were selectively reduced by the non-competitive GABA(A) antagonist picrotoxin (5 microM), but were unaffected by the GABA(B) antagonist 2-hydroxysaclofen (500 microM). Responses evoked by the selective GABA(B) receptor agonist baclofen were not sufficiently large to analyse. The GABA uptake inhibitor, nipecotic acid (500 microM), potentiated responses to GABA, but not to muscimol. Similarly, 10-1000 nM delta-9-THC had no significant effect on the response to muscimol, whereas 1000 nM delta-9-THC significantly increased the response to GABA. Since GABA is the substrate of an avid uptake system, but muscimol is not, the results are consistent with the suggestion that delta-9-THC inhibits the uptake of GABA in the hippocampus.

Altered brain protein kinase C in depression: a post-mortem study.

[(3)H]Phorbol 12,13-dibutyrate (PDBu) binding was measured in soluble and particulate fractions of frontal cortex and hippocampus from suicides, with a firm retrospective diagnosis of depression, and individually matched controls. Suicides were divided into those who had been free of antidepressant drugs for at least 3 months and those in whom prescription of antidepressants was clearly documented. In frontal cortex, there was a significantly higher number (by 75%) of [(3)H]PDBu binding sites in the soluble fraction in antidepressant-free suicides compared to controls; significant differences were also seen in the proportion of sites in the soluble and particulate fractions. Higher numbers of [(3)H]PDBu binding sites in the particulate fraction of hippocampus in antidepressant-free suicides was restricted to those who died by violent means. No significant differences in the number of [(3)H]PDBu binding sites were found in antidepressant-treated suicides compared to controls. This study provides evidence for the involvement of protein kinase C in the pathophysiology of depression.