Induction of shock-selfadministration by benzodiazepines

Induction of shock-selfadministration by benzodiazepines

319 INDUCTION OF SHOCK-SELFADMINISTRATIONBY BENEODIAEBPINES T.F. MEERT and F.C. COLPAERT Department of Psychopharmacology,Janssen Pharmaceutics Rese...

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319

INDUCTION OF SHOCK-SELFADMINISTRATIONBY BENEODIAEBPINES

T.F. MEERT and F.C. COLPAERT Department of Psychopharmacology,Janssen Pharmaceutics Research Laboratories, B-2340 Beerse. Belgium.

A new conflict test was designed to overcome some of the problems that occur with classical conflict models.

In this shock-selfadministrationpro-

cedure, the number of shocks that are selfadministeredby rats in a 5-min test session, is determined. Shock was delivered each time the animal made contact between two uninsulated wires that were wrapped around a Teflon probe inserted into the test box. Of 111 saline treated animals (s.c., 60 min before test) that were tested at a shock intensity of 0.9 mA, only one rat did not initiate the response, and was excluded from data analysis.

The other rats yielded a bell-shaped

frequency distribution with a mean (2 S.E.H.) of 3.57 (+ 0.16) shocks. A shock intensity-response gradient was generated using 0.0. 0.1, 0.9, and 1.7 mA. The mean number of shocks decreased as a function of shock intensity in saline treated (normal control) rats.

With 40 mg/kg of chlordiasepoxide (s.c., 60

min before test). however, no decrement was found. The drug thus completely abolished the response inhibition that otherwise resulted from electric shock. To test the specificity of the procedure,a number of compounds were tested including 5-HT-antagonists,anaigesics. neuroleptics. antidepressants.amphetamine, monoamine oxidase-inhibitors and

O- and

B-blockers.

ED50-values

could only be calculated for benzodiazepines, barbiturates and related compounds.

Pirenperone and ritanserin. two LSD-antagonists. were essentially

inactive in this paradigm. High Spear-manrank correlation coefficients were obtained between data of this paradigm, and data described in the literature of other conflict tests, used to predict anxiolytic drug activity, and of clinically used doses. The shock-selfadministrationprocedure appears to be an accessible conflict model that can be carried out on a single day; it requires neither deprivation nor training, and reveals a high degree of specificity.