ISSN:
1432-2072
Keywords:
κ opioids
;
Drug discrimination
;
Serotonin
;
p-CPA
;
Pigeons
;
8-OH-DPAT
;
NAN-190
;
Buspirone
;
Ketanserin
;
Spiradoline
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects ofκ opioids. Pigeons were trained to discriminate 5.6 mg/kg of theκ opioid, U50,488, from water. During substitution tests, both U50,488 and anotherκ opioid, spiradoline, produced 〉80% responding on the U50,488-appropriate key. In contrast, the nonopioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001–3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01–1 mg/kg), in a dose-dependent manner. Buspirone (0.01–10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT withp-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced byκ opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum ofκ opioid discriminative stimulus effects.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02257409
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