Modulation of Δ9-THC-induced increase of cortical and hippocampal acetylcholine release by μ opioid and D1 dopamine receptors

The administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and synthetic cannabinoids stimulates acetylcholine (ACh) release in the rat prefrontal cortex (PFCx) and hippocampus as estimated by brain microdialysis. The present study was aimed at assessing whether the ability of Delta(9)-THC to stimulate ACh release is dependent upon opioid and dopamine (DA) receptors. Administration of the mu opioid receptor antagonists naloxone and naltrexone prevented the Delta(9)-THC-induced release of ACh in the PFCx and hippocampus. Similarly, bilateral infusion in the ventral tegmental area (VTA). 24 h before Delta(9)-THC, of the pseudo-irreversible mu(1), antagonist naloxonazine completely prevented the increase of ACh release by Delta(9)-THC. Pre-treatment with the D, receptor antagonist SCH 39166 reduced Delta(9)-THC-induced ACh release both in the PFCx and in the hippocampus. Since A9-THC has been shown to increase DA release in the nucleus accumbens (NAc) shell via a mu(1)-opioid receptor mediated mechanism located in the VTA (Tanda, G., Pontieri, F.E., Di Chiara, G., 1997. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu(1) opioid receptor mechanism. Science 276, 2048-2050.), we hypothesize that Delta(9)-THC-induced stimulation of ACh release in the PFCx and hippocampus is related to stimulation of endogenous opioids release in the VTA with secondary activation of DA neurons projecting to the NAc shell. (c) 2005 Elsevier Ltd. All rights reserved.