Neuroleptic-induced changes in the anxiolytic and myorelaxant properties of diazepam in the rat

Harald K. Taukulis, Mark T. Fillmore, Janice L. Ruggles

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Diazepam (2.0 mg/kg) was injected (IP) into rats 30 min before chlorpromazine (2.5, 5.0, or 10.0 mg/kg) on ten occasions. All doses of chlorpromazine enhanced the capacity of diazepam to increase rats' exploration of the exposed arms of an elevated plus-maze, an animal screening test for anxiolytic and anxiogenic substances. When maze testing occurred during each of the ten diazepam → chlorpromazine trials (after diazepam but before chlorpromazine), this enhancement effect appeared on Trial 6 and persisted thereafter. Haloperidol (3.0 mg/ kg. IP) changed diazepam-elicited plus-maze activity in the same manner as chlorpromazine; however, thioridazine (10.0 mg/kg) and pimozide (2.0 mg/kg) were ineffective. Additionally, haloperidol, like chlorpromazine, was found to reduce diazepam's muscle relaxation effect (inclined plane test) as a consequence of diazepam → haloperidol pairings; once again, thioridazine and pimozide proved ineffective. These results suggested that not all neuroleptics will alter diazepam activity, and also that dopamine blockade per se is not sufficient to induce such changes. While the reasons for the enhanced plus-maze effects of diazepam induced by haloperidol and chlorpromazine remain elusive, the diminished myorelaxant effect may be linked to a neuroleptic's capacity to induce muscular side effects; thioridazine and pimozide are far less likely to yield such effects than are chlorpromazine and haloperidol. Haloperidol administered chronically by itself was found to have an effect on diazepam-induced myorelaxation. Administration of this butyrophenone either orally (2.0 mg/kg daily for 22 days) or in depot form (haloperidol decanoate, 60.0 mg/kg IM once a month for four months) caused a diminished effect of diazepam in rats subjected to the inclined plane test. Research into this phenomenon may yield insights into the nature of the diminution of diazepam myorelaxation that results from diazepam → haloperidol pairings.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Jan 1992

Bibliographical note

Funding Information:
This research was supported by Grant 0002027 from the Natural Sciences and Engineering Research Council of Canada to the first author. We are grateful to Claire Goggin, Ralph McKay and Ruth Morrison for assistance with various aspects of these experiments, and to Mary Holland and Karen Keating for assistance with preparation of the manuscript. McNeil Pharmaceutical (Canada) generously provided injectable and oral haloperidol (Haldol) as well as haloperidol decanoate (Haldol LA).


  • Anxiolytic
  • Chlorpromazine
  • Conditioning
  • Diazepam
  • Haloperidol
  • Haloperidol decanoate
  • Inclined plane
  • Interactions
  • Myorelaxant
  • Pimozide
  • Plus-maze
  • Thioridazine

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


Dive into the research topics of 'Neuroleptic-induced changes in the anxiolytic and myorelaxant properties of diazepam in the rat'. Together they form a unique fingerprint.

Cite this