Pharmacological characterization of the enhancement of apomorphine-induced gnawing in mice by cocaine.
The present study was designed to provide additional information on the behavioral and pharmacological mechanisms associated with the augmentation of apomorphine-induced gnawing in C57BL/6J mice. (-)-Cocaine enhanced apomorphine-induced gnawing at doses devoid of effects on gnawing when given alone. The effect was stereoselective, with (+)-cocaine devoid of activity in this test. Peripheral synapses may also not be critical to the cocaine enhancement, as cocaine methiodide, a charged species, was also without effect. The local anesthetic actions of cocaine were evaluated with lidocaine, a local anesthetic without prominent dopaminergic actions. Like (-)-cocaine, lidocaine augmented the gnawing response to apomorphine without increasing climbing or gnawing when given alone. (+)-Amphetamine enhanced apomorphine-induced gnawing but only at a high dose that increased gnawing by itself. The selective dopamine uptake blocker. GBR 12909, augmented apomorphine-induced gnawing without increasing gnawing when given alone; however, unlike cocaine or lidocaine, GBR 12909 increased climbing at doses that augmented the gnawing response. These data indicate that the cocaine-augmented gnawing response to apomorphine does not appear to be the result of psychomotor stimulation per se. Rather, this effect may be due to blockade of dopamine uptake and/or the local anesthetic actions of cocaine.
Tirelli
E
E
Psychobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Witkin
J M
JM
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013239:Stereotyped Behavior / Q000187:drug effects*
D000779:Anesthetics, Local; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D008012:Lidocaine; D003042:Cocaine; D001058:Apomorphine; D003913:Dextroamphetamine