Time-dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats

Janet Neisewander, I. Lucki, P. McGonigle

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The effects of withdrawal from continuous administration of cocaine on behavioral sensitivity to apomorphine and monoamine receptor density were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 2 weeks. Apomorphine- induced stereotypy (0.5 mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60 days after removal of the minipumps. Transient enhanced sensitivity to apomorphine-induced stereotypy occurred during the course of withdrawal. Animals withdrawn from cocaine for 4 hours did not differ from controls in their sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days exhibited an increase in apomorphine- induced oral stereotypy relative to controls. However, the enhanced stereotypy response was no longer evident in animals withdrawn for 28-60 days. The animals were sacrificed after behavioral testing, and their brains were assayed for changes in monoamine receptor density in the frontal cortex, caudate-putamen, and nucleus accumbens. The density of 3H-SCH-23390-labeled D1 receptors was altered in all three regions examined in a time-dependent manner that paralleled the changes in behavioral sensitivity to apomorphine. There was a transient decrease in D1 receptor density that was evident by 7 days following withdrawal from continuous cocaine administration and was no longer evident 28 or 60 days posttreatment. There were no changes in 3H- spiroperidol-labeled D2 receptors, 125-pindolol-labeled β-adrenergic receptors, or 3H-ketanserin-labeled 5-HT2 receptors in any of the regions examined at both 4 hr and 7 days after termination of the cocaine infusion. These findings are discussed in terms of their relevance to developing pharmacologic treatments for withdrawal from cocaine.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalSynapse
Volume16
Issue number1
DOIs
StatePublished - 1994

Fingerprint

Apomorphine
Cocaine
Pindolol
Spiperone
Ketanserin
Caudate Nucleus
Putamen
Nucleus Accumbens
Frontal Lobe
Adrenergic Receptors
Brain

Keywords

  • β-adrenergic receptors
  • 5-HT receptors
  • Chronic administration
  • Continuous administration
  • Dopamine D1 receptors
  • Dopamine D2 receptors
  • Locomotion
  • Sensitization
  • Stereotypy
  • Time course

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Time-dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats. / Neisewander, Janet; Lucki, I.; McGonigle, P.

In: Synapse, Vol. 16, No. 1, 1994, p. 1-10.

Research output: Contribution to journalArticle

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