Article
Behavioral sensitization, behavioral tolerance, and increased [3H]WIN 35,428 binding in rabbit caudate nucleus after repeated injections of cocaine

https://doi.org/10.1016/0091-3057(95)00101-2Get rights and content

Abstract

This study examined whether changes in the behavioral response to repeated intravenous injections of cocaine hydrochloride (4 mg/kg, twice daily for 22 days) might be related to alterations in the dopamine (DA) transporter as measured by the binding of the potent cocaine analog [3H]WIN 35,428 to membranes derived from fresh caudate tissue. Rabbits demonstrated both tolerance and sensitization. Tolerance occurred for cocaine elicited convulsions, whereas sensitization occurred to the ability of cocaine to elicit motor activity, facial twitches, and head bobbing. Cocaine-exposed animals demonstrated a significant 17% increase in the Bmax of specific [3H]WIN 35,428 binding to caudate membranes with no change in Kd. The increase in Bmax was observed at 42 but not 96 h after the last chronic cocaine administration. There was no change in [3H]WIN 35,428 binding at 42 h after a single injection of cocaine. We suggest that the upregulation of the dopamine transporter in the caudate nucleus reflected the mechanisms involved in tolerance rather than sensitization.

References (49)

  • K.Y. Little et al.

    Cocaine use increases [3H]WIN 35428 binding sites in human striatum

    Brain Res.

    (1993)
  • P.J. Munson et al.

    LIGAND: A versatile computerized approach for characterization of ligand-binding systems

    Anal. Biochem.

    (1980)
  • L.C. Nicolaysen et al.

    Extracellular cocaine and dopamine concentrations are linearly related in rat striatum

    Brain Res.

    (1988)
  • M.E.A. Reith

    Effect of repeated administration of various doses of cocaine and WIN 35, 065-2 on locomotor behavior of mice

    Eur. J. Pharmacol.

    (1986)
  • M.E.A. Reith et al.

    Evidence for mutually exclusive binding of cocaine, BTCP, GBR 12935, and dopamine to the dopamine transporter

    Eur. J. Pharmacol.

    (1992)
  • E. Richelson et al.

    Blockade by antidepressants and related compounds of biogenic amine uptake in rat brain synaptosomes: Most antidepressants selectively block norepinephrine uptake

    Eur. J. Pharmacol.

    (1984)
  • M.E. Alburges et al.

    Alterations in the dopaminergic receptor system after chronic administration of cocaine

    Synapse

    (1993)
  • V.J. Aloyo et al.

    [3H]WIN 35,428 binding in the caudate nucleus of the rabbit: Evidence for a single site on the dopamine transporter

    J. Pharmacol. Exp. Ther.

    (1995)
  • J. Bergman et al.

    Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys

    J. Pharmacol. Exp. Ther.

    (1989)
  • E.J. Cline et al.

    Behavioral effects of novel cocaine analogs: A comparison with in vivo receptor binding potency

    J. Pharmacol. Exp. Ther.

    (1992)
  • K.A. Cunningham et al.

    Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding

    Synapse

    (1992)
  • J.M. Delfs et al.

    Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat

    J. Neurosci.

    (1990)
  • P.W. Kalivas et al.

    Time course of extracellular dopamine and behavioral sensitization to cocaine. I. Dopamine axon terminals

    J. Neurosci.

    (1993)
  • J.L. Katz et al.

    Cocaine tolerance and cross-tolerance

    J. Pharmacol. Exp. Ther.

    (1993)
  • Cited by (0)

    View full text