Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking

S Erb, P K Hitchcott, H Rajabi, D Mueller, Y Shaham, J Stewart*

*Corresponding author for this work

Research output: Contribution to JournalArticlepeer-review

Abstract

The alpha-2 adrenergic receptor agonists, clonidine, lofexidine and guanabenz, blocked stress- but not cocaine-induced reinstatement of cocaine seeking at doses that suppressed footshock-induced release of noradrenaline in prefrontal cortex and amygdala. Rats were trained to self-administer cocaine (0.5 mg/kg/infusion, i.v; 10-12 days) and, after a drug-free period (7-13 days), were returned to the self-administration chambers for daily extinction and reinstatement test sessions. Both intermittent footshock (15 min, 0.6 mA) and cocaine priming (20 mg/kg, i.p.) reinstated extinguished drug seeking. Pretreatment with either clonidine (20, or 40 microg/kg, i.p.) or lofexidine (50, 100, 150, or 200 microg/kg, i.p.) attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. Guanabenz (640 microg/kg, i.p.), an alpha-2 agonist with low affinity for imidazoline type-1 receptors, also attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. The results point to an important role for NE systems in the effects of footshock on relapse to cocaine seeking.

Original languageEnglish
Pages (from-to)138-150
Number of pages13
JournalNeuropsychopharmacology
Volume23
Issue number2
DOIs
Publication statusPublished - Aug 2000
Externally publishedYes

Keywords

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists/therapeutic use
  • Animals
  • Catheterization
  • Clonidine/administration & dosage
  • Cocaine/administration & dosage
  • Cocaine-Related Disorders/complications
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Guanabenz/administration & dosage
  • Infusions, Intravenous
  • Injections, Intraperitoneal
  • Male
  • Microdialysis
  • Narcotic Antagonists/therapeutic use
  • Norepinephrine/analysis
  • Rats
  • Rats, Long-Evans
  • Self Administration
  • Stress, Physiological/complications
  • Sucrose/administration & dosage

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