The rate of intravenous cocaine administration determines susceptibility to sensitization.
The potential for addiction is thought to be greatest when drugs of abuse reach the brain rapidly, because this produces intense subjective pleasurable effects. However, the ability of drugs to induce forms of cellular plasticity related to behavioral sensitization may also contribute to addiction. Therefore, we studied the influence of rate of intravenous cocaine delivery on its ability to induce psychomotor sensitization. In one experiment, rotational behavior in rats with a unilateral 6-hydroxydopamine lesion was used as an index of psychomotor activation, and in a second experiment, locomotor activity in neurologically intact rats was used. Rapid (5-16 sec) intravenous infusions of cocaine induced robust psychomotor sensitization at all doses tested (0.5-2.0 mg/kg). Treatments given over 25 sec failed to induce sensitization at all doses tested. Treatments given over 50 or 100 sec induced sensitization only at the highest dose tested. Thus, the rate of intravenous cocaine delivery has profound effects on the ability of cocaine to induce psychomotor sensitization. This suggests that the temporal dynamics of drug delivery to the brain is a critical factor in the ability of cocaine to induce forms of neuronal plasticity that may contribute to addiction.
Samaha
Anne-Noel
AN
Department of Psychology (Biopsychology Program), The University of Michigan, Ann Arbor, Michigan 48109-1109, USA.
Li
Yilin
Y
Robinson
Terry E
TE
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007275:Injections, Intravenous; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016627:Oxidopamine; D003042:Cocaine; D001058:Apomorphine