Levonantradol‐Induced Inhibition of Acetylcholine Turnover in Rat Hippocampus and Striatum

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Abstract
The effects of levonantradol, a structurally novel cannabinoid‐related analgesic, on the turnover rate of acetylcholine (TRACh) have been studied in various regions of the rat brain. Levonantradol (0.3 mg/kg subcutaneously) decreases the TRACh in the hippocampus and striatum by 53 and 30 per cent, respectively. The extent of the reduction in TRAch is dose dependent, with a maximal decrease of 80 per cent in the hippocampus and 57 per cent in the striatum following the 3 mg/kg dose. In contrast, cortical TRAch is not affected by any dose of levonantradol. This pattern of activity on cholinergic dynamics elicited by levonantradol is qualitatively similar to that of cannabinoids but differs from that previously reported for narcotic analgesics. Moreover, naltrexone (2 mg/kg intraperitoneally) does not reverse the effects of levonantradol on striatal or hippocampal TRAch. This pattern of activity on cholinergic dynamics elicited by levonantradol is consistent with a cannabinoid‐like rather than an opioid‐like mode of action.