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-administratio n, Wistar rats were allowed to self-administer various doses of nicotine us ing a within-subjects Latin square design. An inverted U-shaped dose-respon se 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 o f somatic signs of withdrawal after subcutaneous injection of a nicotinic a cetylcholine receptor antagonist, mecamylamine (0.57 mg/kg). In another set of studies, pretreatment with subcutaneous mecamylamine or dihydro-beta-er ythroidine, two nicotinic acetylcholine receptor antagonists, resulted in s ignificant dose-dependent reductions in nicotine self-administration, at tw o nicotine doses (0.03 and 0.06 mg/kg/inf). These results indicate that nic otine is an effective reinforcer in Wistar rats under the present parameter s, and that these reinforcing effects are mediated by activation of nicotin ic acetylcholine receptors. (C) 1999 Elsevier Science Inc.