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Diazepam-induced place preference conditioning: Appetitive and antiaversive properties

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Abstract

The place conditioning paradigm was used to examine the reinforcing properties of diazepam. Rats were injeccted with diazepam (0.5–5.0 mg/kg, IP) and 30 min later were confined for 30 min to one side of a shuttle box, in which each of the two compartments had distinctive features. On alternate (control) days they received vehicle injections and were confined for 30 min to the opposite side. At almost all doses tested, diazepam produced place preference for the distinctive compartment that had been previously associated with the drug. Preference for the drug side developed regardless of whether diazepam was paired or unpaired with the least-preferred side, and regardless of whether testing was carried out in the undrugged or in the drugged state. The rats preferred the drug side over a novel compartment, but they did not change their initial preference for the side when diazepam was given after removal from the training box.

Animals injected with meprobamate (70 mg/kg, PO), a non-benzodiazepine anxiolytic, also developed conditioned preference for the drug side, comparable to that seen following cocaine hydrochloride (10 mg/kg, IP).

The diazepam (2.5 mg/kg)-induced place preference was antagonized by CGS 8216 (3 mg/kg, IP), picrotoxin (2 mg/kg, IP) and naloxone (0.8 mg/kg, SC), injected 3 min before and 15 and 20 min after diazepam respectively. Sodium valproate (200 mg/kg, IP) did not influence diazepam (1 mg/kg)-induced place preference. Sodium valproate by itself had marginal effects on place conditioning. Picrotoxin and naloxone, but not CGS 8816, produced place aversion which, in the case of picrotoxin, was due to state dependent learning. The results provide a clear indication that the place preference paradigm is valid as a test for evaluating appetitive properties of minor tranquilizers. They suggest that the rewarding effects of diazepam are mediated through central benzodiazepine receptors. Wheter GABA and/or endogenous opioid peptides are involved in the reinforcing properties of diazepam remains an open question.

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Authors and Affiliations

  1. Department of Experimental Pharmacology, Medical School, University of Athens, Goudi, 11527, Athens, Greece

    Christina Spyraki, Anna Kazandjian & Denis Varonos

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  1. Christina Spyraki
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  2. Anna Kazandjian
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  3. Denis Varonos
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Additional information

A preliminary report of this research was made at the 14 C.I.N.P. Congress (Florence 1984)

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Spyraki, C., Kazandjian, A. & Varonos, D. Diazepam-induced place preference conditioning: Appetitive and antiaversive properties. Psychopharmacology 87, 225–232 (1985). https://doi.org/10.1007/BF00431813

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  • DOI: https://doi.org/10.1007/BF00431813

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