Mecamylamine but not the alpha 7 receptor antagonist alpha-bungarotoxin blocks sensitization to the locomotor stimulant effects of nicotine

1 The involvement of alpha7 receptors in the locomotor stimulant effects of nicotine has been examined by determining the ability of intracerebroventr icular (i.c.v.) administration of the alpha7 receptor antagonist alpha -bun garotoxin (alpha -bgt) to modify sensitization to the locomotor activating effects of chronic nicotine. 2 Intracerebroventricular administration of alpha -bgt (0.02-8 nmoles) prod uced a dose dependent increase in convulsive behaviour. At doses less than 1.0 nmole, minimal convulsive behaviour occurred but larger doses evoked co nvulsions in all rats which displayed a more rapid onset time as the dose i ncreased. 3 The binding distribution of alpha7 receptors 20 min and 3 h following an i.c.v. administration of [I-125]-alpha -bgt (0.02 nmoles) revealed clear bi nding in the hippocampus, cingulate cortex and hypothalamus which was more intense after 3 h. 4 Rats chronically treated with nicotine (0.4 mg kg(-1)) and exposed to the locomotor activity apparatus daily acquired an increase in locomotor activ ity relative to the control group after 3 days of treatment which reached a maximum after 7 days of treatment and was maintained for the 2 week treatm ent period. 5 Pre-treatment with mecamylamine (1 mg kg(-1)) prevented the expression of the locomotor stimulant effects of nicotine but pre-treatment with i.c.v. alpha -bgt (0.02 nmoles) did not affect nicotine-induced changes in locomot or activity. 6 The results of this study support the conclusion that nicotinic receptors of the alpha4 beta2 subtype rather than the alpha7 subtype are important i n mediating the expression of the locomotor stimulant effects of nicotine.