Discriminative stimulus properties of xylazine in rat: discriminability and effects of putative alpha-2 adrenoceptor agonists and antagonists.
In a first experiment, rats were trained initially to discriminate i.p. injections of 2.5 mg/kg of xylazine from saline in a two-lever, food-reinforced, fixed-ratio 10 drug discrimination procedure. The animals were then retrained on progressively lower doses of the training drug. The stimulus generalization gradient of xylazine was established each time the animals had reached criterion on successive training doses; the criterion required that lever selection be appropriate to the saline or xylazine injection on 10 consecutive sessions. The findings indicate the lowest xylazine training dose at which individual rats can reach criterion to range from 2.5 to less than or equal to 0.31 mg/kg; the median lowest discriminable dose was 0.89 mg/kg. The distribution of lowest discriminable dose accommodated a Gaussian shape. The slope of the xylazine gradient did not in a systematic manner vary as a function of training dose, and the ED50 value of xylazine was an almost constant fraction of training dose (1:2.0) at training doses ranging from 2.5 to 0.63 mg/kg. A second experiment examined the xylazine-like agonist and the xylazine-antagonist effects of clonidine, yohimbine, piperoxan and idazoxan in rats discriminating xylazine from saline at a training dose of 2.5 mg/kg. Clonidine produced generalization in all animals and antagonized the xylazine stimulus in one. Idazoxan produced near complete antagonism, and was generalized in one animal. Yohimbine and piperoxan produced magnitudes of agonist and antagonist effects that were intermediate between those of clonidine and idazoxan. Lisuride and d-lysergic acid diethylamide produced up to 71 and 29% generalization, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Colpaert
F C
FC
Janssen
P A
PA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D019329:Idazoxan; D008090:Lisuride / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010883:Piperoxan / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013843:Thiazines / Q000494:pharmacology*; D014991:Xylazine / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D013843:Thiazines; D014991:Xylazine; D015016:Yohimbine; D008238:Lysergic Acid Diethylamide; D010883:Piperoxan; D008090:Lisuride; D003000:Clonidine; D019329:Idazoxan