Modulation of Δ 9-THC-induced increase of cortical and hippocampal acetylcholine release by μ opioid and D 1 dopamine receptors

Abstract

The administration of Δ 9-tetrahydrocannabinol (Δ 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 Δ 9-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 Δ 9-THC-induced release of ACh in the PFCx and hippocampus. Similarly, bilateral infusion in the ventral tegmental area (VTA), 24 h before Δ 9-THC, of the pseudo-irreversible μ 1 antagonist naloxonazine completely prevented the increase of ACh release by Δ 9-THC. Pre-treatment with the D 1 receptor antagonist SCH 39166 reduced Δ 9-THC-induced ACh release both in the PFCx and in the hippocampus. Since Δ 9-THC has been shown to increase DA release in the nucleus accumbens (NAc) shell via a μ 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 μ 1 opioid receptor mechanism. Science 276, 2048–2050.), we hypothesize that Δ 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.