Neuroleptics block high- but not low-dose heroin place preferences: further evidence for a two-system model of motivation

Behav Neurosci. 1994 Dec;108(6):1128-38. doi: 10.1037//0735-7044.108.6.1128.

Abstract

The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brainstem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Avoidance Learning / drug effects
  • Brain Mapping
  • Brain Stem / drug effects*
  • Brain Stem / physiopathology
  • Conditioning, Classical / drug effects*
  • Dopamine / physiology
  • Dose-Response Relationship, Drug
  • Flupenthixol / pharmacology
  • Heroin / antagonists & inhibitors*
  • Heroin / pharmacology
  • Heroin Dependence / physiopathology
  • Male
  • Motivation*
  • Pimozide / pharmacology
  • Premedication
  • Rats
  • Rats, Wistar
  • Social Environment*
  • Substance Withdrawal Syndrome / physiopathology
  • Synaptic Transmission / drug effects

Substances

  • Antipsychotic Agents
  • Pimozide
  • Heroin
  • Flupenthixol
  • Dopamine