A novel nicotinic-cholinergic role in behavioral sensitization to amphetamine-induced stereotypy in mice.
Cholinergic antagonists were used to investigate the role of the cholinergic system in amphetamine- and cocaine-induced behavioral sensitization to stereotypy in mice. Systemically, mecamylamine (1 mg/kg) and dihydro-beta-erythroidine (2 mg/kg) - nicotinic antagonists - and atropine (2 mg/kg) - a muscarinic antagonist - were ineffective against psychostimulant-induced stereotypy in naive animals. The nicotinic antagonists, however, blocked both the induction and expression of sensitization to amphetamine; in contrast, atropine was ineffective. All three drugs were ineffective against either the induction or expression of cocaine sensitization. Intrastriatally, the nicotinic antagonists blocked induction but not expression of amphetamine-induced sensitization. The results suggest that the nicotinic system participates in sensitization induced by amphetamine but not cocaine; that the nicotinic component of the amphetamine response in sensitized animals is novel as compared to the response in naive animals; and that the striatum is a locus for the nicotinic involvement in induction but not expression. The data add support to the inference that behavioral sensitization represents not only a quantitative but a qualitative change in response to amphetamine.
Karler
R
R
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Calder
L D
LD
Bedingfield
J B
JB
D000109:Acetylcholine / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D018680:Cholinergic Antagonists; D018765:Dopamine Uptake Inhibitors; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D001285:Atropine; D000661:Amphetamine; D003042:Cocaine; D000109:Acetylcholine