<b>Aim:</b> Δ<sup>9</sup>-Tetrahydrocannabinol (Δ<sup>9</sup>-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) ...<b>Aim:</b> Δ<sup>9</sup>-Tetrahydrocannabinol (Δ<sup>9</sup>-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ<sup>9</sup>-THC in mice and whether Δ<sup>9</sup>-THC had any impact <i>ex-vivo</i> and <i>in-vitro</i> on NAT activity. <b>Methods:</b> Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ<sup>9</sup>-THC (0.10, 0.50 or 2.0 mg/kg/mL, <i>ip</i>) or amphetamine (AMP, 5.0 mg/kg/mL, <i>ip</i>);while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ<sup>9</sup>-THC treated and untreated mice were excised and NAT enzyme activity determined <i>ex-vivo</i> using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ<sup>9</sup>-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated <i>in-vitro</i>. <b>Results:</b> Δ<sup>9</sup>-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). Mice treated with 2.0 mg/kg Δ<sup>9</sup>-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AMP-treated mice displayed significant (p < 0.001) increases in both entries and time spent in the drug-paired chamber at post-conditioning (positive place preference). <i>In-vitro</i> NAT evaluations revealed a dose-dependent inhibitory impact of Δ<sup>9</sup>-THC on NAT activity with an IC50 value of 34展开更多
文摘<b>Aim:</b> Δ<sup>9</sup>-Tetrahydrocannabinol (Δ<sup>9</sup>-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ<sup>9</sup>-THC in mice and whether Δ<sup>9</sup>-THC had any impact <i>ex-vivo</i> and <i>in-vitro</i> on NAT activity. <b>Methods:</b> Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ<sup>9</sup>-THC (0.10, 0.50 or 2.0 mg/kg/mL, <i>ip</i>) or amphetamine (AMP, 5.0 mg/kg/mL, <i>ip</i>);while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ<sup>9</sup>-THC treated and untreated mice were excised and NAT enzyme activity determined <i>ex-vivo</i> using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ<sup>9</sup>-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated <i>in-vitro</i>. <b>Results:</b> Δ<sup>9</sup>-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). Mice treated with 2.0 mg/kg Δ<sup>9</sup>-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AMP-treated mice displayed significant (p < 0.001) increases in both entries and time spent in the drug-paired chamber at post-conditioning (positive place preference). <i>In-vitro</i> NAT evaluations revealed a dose-dependent inhibitory impact of Δ<sup>9</sup>-THC on NAT activity with an IC50 value of 34
