Lack of evidence for appetitive effects of Δ9-tetrahydrocannabinol in the intracranial self-stimulation and conditioned place preference procedures in rodents

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Data on the ability of Δ9-tetrahydrocannabinol (THC) to modify reward processes in experimental animals are inconsistent. This study examined the effects of Δ9-THC on brain reward function using the rate–frequency curve shift paradigm of intracranial self-stimulation (ICSS) and the conditioned place preference (CPP) paradigm. In ICSS tests, rats were implanted with electrodes into the medial forebrain bundle. After brain stimulation reward thresholds stabilized, rats received intraperitoneal injections of Δ9-THC (0, 0.5, 1 and 2 mg/kg) or the CB1 receptor antagonist SR141716A (0, 0.02 mg/kg) and Δ9-THC (0, 2 mg/kg). The two highest doses of Δ9-THC significantly increased the threshold ICSS frequency. SR141716A reversed the action of Δ9-THC (2 mg/kg), without affecting reward thresholds by itself. In the CPP test, mice received intraperitoneal injections of Δ9-THC (0, 1 or 3 mg/kg). Δ9-THC showed neither statistically significant preference nor aversion in either of the doses tested. These findings indicate that Δ9-THC, in contrast to other drugs of abuse, does not facilitate ICSS or support CPP under the present experimental conditions, but rather has a dose-dependent inhibitory influence on ICSS.

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