Nicotine-, tobacco particulate matter- and methamphetamine-produced locomotor sensitisation in rats

Abstract

Repeated nicotine exposure produces a weak and transient sensitised locomotor response in rats. Since tobacco smoke contains thousands of non-nicotine chemical constituents, these could alter the sensitised response. This study aims to compare the magnitude, persistence and spatial distribution of locomotor sensitisation produced by repeated doses of nicotine, aqueous tobacco particulate matter (TPM) and a positive methamphetamine control. Male Sprague-Dawley rats received five nicotine (0.0, 0.2 or 0.4mg/kg), TPM (containing 0.2 or 0.4mg/kg nicotine) or methamphetamine (0.5mg/kg) injections every second day, followed by a 4-day withdrawal before the first challenge (Challenge 1, C1). The animals were re-challenged again at 15days post C1 to test for the persistence of sensitisation (Challenge 2, C2). There were no major differences in sensitisation profile between nicotine and TPM. At the lowest 0.2mg/kg nicotine/TPM dose, however, small differences emerged on select test days. The results indicated that the non-nicotinic agents in TPM did not greatly impact the nicotine-produced locomotor-sensitised response. These findings might suggest that the differential pharmacological properties of TPM do not have major clinical significance. Alternatively, the locomotor model might not expose effects of non-nicotinic constituents, and furthermore, might not closely relate to human tobacco dependence. Different reward-related behavioural models should also be utilised to assess potential effects of non-nicotinic constituents before a role in dependence is discounted.