Mecamylamine but not the alpha7 receptor antagonist alpha-bungarotoxin blocks sensitization to the locomotor stimulant effects of nicotine.
The involvement of alpha7 receptors in the locomotor stimulant effects of nicotine has been examined by determining the ability of intracerebroventricular (i.c.v.) administration of the alpha7 receptor antagonist alpha-bungarotoxin (alpha-bgt) to modify sensitization to the locomotor activating effects of chronic nicotine. Intracerebroventricular administration of alpha-bgt (0.02 - 8 nmoles) produced a dose dependent increase in convulsive behaviour. At doses less than 1.0 nmole, minimal convulsive behaviour occurred but larger doses evoked convulsions in all rats which displayed a more rapid onset time as the dose increased. The binding distribution of alpha7 receptors 20 min and 3 h following an i.c.v. administration of [(125)I]-alpha-bgt (0.02 nmoles) revealed clear binding in the hippocampus, cingulate cortex and hypothalamus which was more intense after 3 h. Rats chronically treated with nicotine (0.4 mg kg(-1)) and exposed to the locomotor activity apparatus daily acquired an increase in locomotor activity 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 treatment period. 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 locomotor activity. The results of this study support the conclusion that nicotinic receptors of the alpha4beta2 subtype rather than the alpha7 subtype are important in mediating the expression of the locomotor stimulant effects of nicotine.
Kempsill
F E
FE
Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Taylor Street, Glasgow G4 ONR.
Pratt
J A
JA
D000818:Animals; D001921:Brain / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*
D002038:Bungarotoxins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine