Different times of withdrawal from cocaine administration cause changes in muscarinic and dopaminergic receptors in rat premotor cortex

Neurosci Lett. 2001 Oct 26;312(3):129-32. doi: 10.1016/s0304-3940(01)02222-4.

Abstract

The present work studied neurochemical changes in rat premotor cortex 30 min, 1 and 5 days after withdrawal from cocaine repeated administration (20 and 30 mg/kg, intraperitoneally, daily for 7 days). Binding assays were performed in 10% homogenates, and ligands used were [(3)H]-N-methylscopolamine, [(3)H]-SCH 23390, and [(3)H]-spiroperidol for muscarinic, D(1)- and D(2)-like receptors, respectively. Levels of cyclic AMP (cAMP) and cyclic guanosine monophosphate (cGMP) were determined using a commercial kit. Scatchard analyses of muscarinic receptors showed an upregulation after 1 and 5 days withdrawal. While D(2)-like receptors were upregulated at all withdrawal periods, D(1)-like receptors were upregulated only at the 30 min withdrawal, and returned to normal levels after 1 day of the last injection. In relation to cAMP levels, the repeated cocaine administration, 1 day after the last injection produced a decrease (around 26%) with both doses, while a 67% increase was seen in cGMP levels with the 30 mg/kg dose. These findings indicate lasting neurochemical changes in premotor cortex caused by cocaine which remained after different withdrawal periods.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / physiopathology
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Male
  • Motor Cortex / drug effects*
  • Motor Cortex / metabolism
  • Motor Cortex / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Substance Withdrawal Syndrome / metabolism*
  • Substance Withdrawal Syndrome / physiopathology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Muscarinic
  • Cyclic AMP
  • Cyclic GMP
  • Cocaine