Blockade of nicotine self-administration with nicotinic antagonists in rats

The reinforcing properties of a variety of drugs abused by humans have been investigated using the technique of intravenous self-administration in the rat. To examine the effect of nicotine dose on nicotine self-administration, Wistar rats were allowed to self-administer various doses of nicotine using a within-subjects Latin square design. An inverted U-shaped dose-response curve was obtained, with the highest rates of responding at the 0.03 mg/kg/inf dose. With I-h daily nicotine sell-administration sessions, rats did not appear dependent on nicotine 24 h later, as indicated by the absence of somatic signs of withdrawal after subcutaneous injection of a nicotinic acetylcholine receptor antagonist, mecamylamine (0.57 mg/kg). In another set of studies, pretreatment with subcutaneous mecamylamine or dihydro-beta-erythroidine, two nicotinic acetylcholine receptor antagonists, resulted in significant dose-dependent reductions in nicotine self-administration, at two nicotine doses (0.03 and 0.06 mg/kg/inf). These results indicate that nicotine is an effective reinforcer in Wistar rats under the present parameters, and that these reinforcing effects are mediated by activation of nicotinic acetylcholine receptors. (C) 1999 Elsevier Science Inc.