Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens

Biol Psychiatry. 1986 Jan;21(1):34-48. doi: 10.1016/0006-3223(86)90006-5.


It has previously been demonstrated that direct opiate infusion into nucleus accumbens elicits psychomotor activation in rats. In the present study, the effects of chronic treatment with five different neuroleptics on this behavioral response were investigated. All neuroleptics tested (haloperidol, sulpiride, flupentixol decanoate, perphenazine enanthate, fluphenazine decanoate, palmitic ester of pipotiazine) induced a marked behavioral supersensitivity to intraaccumbens opiate infusion. A similarly enhanced sensitivity was observed in chronic reserpine-treated rats. The maximum sensitivity to opiates appeared 2-3 weeks after the beginning of neuroleptic treatment and was present up to 1 month after the end of treatment. Naloxone blocked the neuroleptic-induced enhanced response to opiates. It is concluded that chronic blockade of dopaminergic transmission results in considerable functional alterations of the endogenous opiate systems. The results are discussed in terms of possible underlying neuronal mechanisms, and important clinical implications are noted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Enkephalin, Methionine / analogs & derivatives*
  • Enkephalin, Methionine / pharmacology
  • Flupenthixol / analogs & derivatives
  • Flupenthixol / pharmacology
  • Fluphenazine / analogs & derivatives
  • Fluphenazine / pharmacology
  • Haloperidol / pharmacology
  • Male
  • Nucleus Accumbens / drug effects*
  • Perphenazine / analogs & derivatives
  • Perphenazine / pharmacology
  • Phenothiazines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Reserpine / pharmacology
  • Septal Nuclei / drug effects*
  • Sulpiride / pharmacology
  • Time Factors


  • Antipsychotic Agents
  • Phenothiazines
  • Receptors, Dopamine
  • flupenthixol decanoate
  • Enkephalin, Methionine
  • enkephalinamide-Met, Ala(2)-
  • Sulpiride
  • Reserpine
  • Flupenthixol
  • fluphenazine depot
  • Perphenazine
  • Haloperidol
  • Fluphenazine
  • perphenazine enanthate