Transient hypersensitivity to apomorphine-induced gnawing after termination of acute effects of a single high dose of cocaine.
Physical dependence on cocaine has not been fully characterized or definitively identified. Since behavioral changes are typically not observed after cocaine withdrawal in animal studies, we sought to amplify or reveal any such changes in behavior by administration of the dopamine agonist apomorphine. C57BL/6J mice were tested for behavioral effects (climbing, gnawing, and locomotor activity) of apomorphine at various times after acute administration of cocaine. When tested at a time when most of the administered cocaine had disappeared from brain and when behavioral effects of cocaine had dissipated, at 2 and 4h post cocaine administration, effects of apomorphine on gnawing were increased 4-fold. This dopaminergic hypersensitivity was induced by acute treatment with doses of 15mg/kg cocaine and higher. Effects of apomorphine were not enhanced at later time periods (6 to 24h after cocaine), indicating a rapid waning of the dopaminergic hypersensitivity. Hypersensitivity to apomorphine was not further augmented by 8 days of daily cocaine injections. Cocaine did not influence climbing and hypomotility induced by apomorphine 4h after its injection, demonstrating selectivity in the behavioral expression of the dopaminergic hypersensitivity. Further, cocaine did not induce sensitization to its own effects indicating that the hypersensitivity to apomorphine was not due to a typical sensitization phenomenon. The results of these experiments demonstrate a short-lived dopaminergic supersensitivity after termination of the acute effects of a single high dose of cocaine, the implications of which remain to be discovered.
Tirelli
E.
E
Drug Development Group, Psychobiology Section, Addiction Research Center, National Institute on Drug Abuse, P.O. Box 5180, Baltimore, MD 21224, USA.
Witkin
J.M.
JM