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

The administration of Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC to stimulate ACh release is dependent upon opioid and dopamine (DA) receptors. Administration of the μ opioid receptor antagonists naloxone and naltrexone prevented the Δ9-THC-induced release of ACh in the PFCx and hippocampus. Similarly, bilateral infusion in the ventral tegmental area (VTA), 24 h before Δ9-THC, of the pseudo-irreversible μ1 antagonist naloxonazine completely prevented the increase of ACh release by Δ9-THC. Pre-treatment with the D1 receptor antagonist SCH 39166 reduced Δ9-THC-induced ACh release both in the PFCx and in the hippocampus. Since Δ9-THC has been shown to increase DA release in the nucleus accumbens (NAc) shell via a μ1-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 μ1 opioid receptor mechanism. Science 276, 2048–2050.), we hypothesize that Δ9-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.