PHARMACOLOGICAL ANALYSIS OF THE PHENCYCLIDINE-LIKE DISCRIMINATIVE STIMULUS PROPERTIES OF NARCOTIC DERIVATIVES IN RATS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 222  (1) , 146-151
Abstract
The phencyclidine (PCP)-like discriminative stimulus properties of narcotic derivatives in the rat were evaluated. Rats were trained to discriminate between saline and 3.0 mg/kg of PCP in a 2-choice, shock-avoidance procedure. PCP-like stimulus control of behavior was produced by (in order of relative molar potency): l-cyclazocine > PCP > dl-cyclazocine > SKF 10,047 [N-allylnormetazocine] > MeO-cyclazocine [3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-2,6-methano-8-methoxy-3-benzazocin base] > dextrorphan > d-cyclazocine. Metazocine and levallorphan also occasioned appreciable percentages of PCP-appropriate responding. Ten other narcotic derivatives [meperidine, nalorphine, l-oxilorphan, nalbuphrine, dl-pentazocine, butorphanol, dl-normetazocine, levorphanol, buprenurphine and l-BC 2910 (l-2''-hydroxy-2(N)-cyclopropyl-methyl-5-propyl-.alpha.-9-methyl-.beta.-9-hydroxy-6,7-benzomorphan)] occasioned only saline-appropriate responding. Among enantiomeric pairs, levocyclazocine was more potent than dextrocyclazocine, and dextrorphan but not levorphanol produced PCP-like discriminative effects. The specific narcotic antagonist naloxone failed to antagonize these PCP-like effects but rather increased the relative potency of cyclazocine and unmasked PCP-like effects of higher doses of metazocine. Apparently, that PCP and selected narcotic derivatives have similar components of action which appear to be mediated by .omega. receptors rather than receptors which subserve the characteristic opioid actions or narcotic analgesics.