Delta9-tetrahydrocannabinol enhances cortical and hippocampal acetylcholine release in vivo: a microdialysis study.

The intravenous administration of synthetic cannabinoid agonists was recently shown to dose dependently increase acetylcholine release from the rat prefrontal cortex and hippocampus (Eur. J. Pharmacol. 401 (2000) 179]. We report here that the active ingredient of cannabis preparations, delta9-tetrahydrocannabinol, administered at 10, 37.5, 75 and 150 microg/kg, dose dependently stimulated acetylcholine release from rat prefrontal cortex and hippocampus estimated by means of in vivo brain microdialysis with vertical concentric probes. At these doses, delta9-tetrahydrocannabinol induced behavioural stimulation. The administration of the CB1 receptor antagonist, ([N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3carboxamide]HCl) SR 141716A (200 microg/kg i.p.) significantly reduced the effect of delta9-tetrahydrocannabinol (75 microg/kg i.v.) on acetylcholine release from rat prefrontal cortex and hippocampus.

Intravenous administration of ecstasy (3,4-methylendioxymethamphetamine) enhances cortical and striatal acetylcholine release in vivo.

The effect of intravenous administration of 3,4-methylendioxymethamphetamine (MDMA), in a range of doses (0.32-3.2 mg/kg) that have been shown to maintain self-administration behaviour in rats, on in vivo acetylcholine release from rat prefrontal cortex and dorsal striatum was studied by means of microdialysis with vertical concentric probes. Intravenous administration of MDMA dose-dependently increased basal acetylcholine release from the prefrontal cortex to 57+/-21%, 98+/-20%, 102+/-7% and 141+/-14% above baseline, at doses of 0.32, 0.64, 1.0 and 3.2 mg/kg, respectively. MDMA also stimulated striatal acetylcholine release at the dose of 3.2 mg/kg i.v. (the maximal increase being 32+/-3% above baseline) while at the dose of 1 mg/kg i.v., MDMA failed to affect basal acetylcholine output. Administration of MDMA also dose-dependently stimulated behaviour. The results of the present study show that MDMA affects measures of central cholinergic neurotransmission in vivo and suggest that at least some of the psychomotor stimulant actions of MDMA might be positively coupled with an increase in prefrontal cortical and striatal acetylcholine release.

Cannabinoid CB(1) receptor agonists increase rat cortical and hippocampal acetylcholine release in vivo.

Intravenous administration of the cannabinoid CB(1) receptor agonists (R-(+)-[2, 3-Dihydro-5-methyl-3[morpholinyl)methyl]-pyrrolo[1,2,3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), WIN 55,212-2 (10, 37.5, 75 and 150 microg/kg), and ((6aR)-trans-3-(1, 1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6, 6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol), HU 210 (1 and 4 microg/kg) dose-dependently increased acetylcholine release in dialysates from the prefrontal cortex and the hippocampus of freely moving rats. Administration of the cannabinoid receptor antagonist [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide]HCl, SR 141716A, at a dose that per se did not affect basal acetylcholine release (2. 5 microg/kg), prevented the increase of acetylcholine release by WIN 55,212-2 (150 microg/kg i.v.) or by HU 210 (4 microg/kg i.v.) in both areas. These data demonstrate that, at low i.v. doses, the synthetic cannabinoid CB(1) receptor agonists, WIN 55,212-2 and HU 210 stimulate cortical and hippocampal acetylcholine release.