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Discriminative stimulus effects of tizanidine hydrochloride: Studies with rats trained to discriminate either tizanidine, clonidine, diazepam, fentanyl, or cocaine
Author(s) -
Shearman Gary T.
Publication year - 1987
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430100105
Subject(s) - tizanidine , clonidine , diazepam , yohimbine , pharmacology , pentobarbital , muscle relaxant , fentanyl , stimulus control , morphine , anesthesia , medicine , antagonist , receptor , nicotine , spasticity
Male Sprague Dawley rats were trained in a two‐lever food‐reinforced procedure to discriminate between the effects of saline and either tizanidine hydrochloride, clonidine hydrochloride, diazepam, fentanyl, or cocaine hydrochloride. Tizanidine‐trained rats dose‐dependently generalized the effects of tizanidine and clonidine but not pentobarbital, diazepam, morphine, or cocaine. Clonidine‐trained rats dose‐dependently generalized the effects of clonidine and tizanidine but not pentobarbital, diazepam, or morphine. Diazepam‐trained rats dose‐dependently generalized the effects of diazepam but did not generalize tizanidine. Fentanyl‐trained rats dose‐dependently generalized the effects of fentanyl but did not generalize tizanidine. Cocaine‐trained rats did not generalize the effects of tizanidine to the cocaine discriminative stimulus. Yohimbine hydrochloride but not naloxone hydrochloride dose‐dependently antagonized the discriminative stimuli produced by both tizanidine and clonidine. These data demonstrate that tizanidine shares discriminative stimulus properties with clonidine but not with pentobarbital, diazepam, fentanyl, morphine, or cocaine. The discriminative stimuli produced by tizanidine and clonidine are mediated via an agonistic interaction with alpha 2 ‐adrenergic receptors and not via an agonistic interaction with opioid receptors.