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Serotonin involvement in the discriminative stimulus effects of κ opioids in pigeons

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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.

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Abbreviations

5HT:

serotonin

8-OH-DPAT:

(±)-8-hydroxy(di-N-propylamino) tetralin hydrobromide

NAN-190:

1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine HBr

DOI:

(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride;

MDL72222:

3-tropanyl-3,5-dichlorobenzoate

mCPP:

1-(3-chlorophenyl) piperazine dihydrochloride

p-PCA:

dl-para-chlorophenylalanine methyl ester

U50, 488:

trans(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide

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  1. Maureen E. Bronson

    Present address: Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Auburn University, 36849-5503, AL, USA

Authors and Affiliations

  1. Department of Psychology, University of North Carolina, Chapel Hill, North Carolina, USA

    Maureen E. Bronson, Yu-Pang Lin & Mitchell J. Picker

  2. Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA

    Kris Burchett & Linda A. Dykstra

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Bronson, M.E., Lin, YP., Burchett, K. et al. Serotonin involvement in the discriminative stimulus effects of κ opioids in pigeons. Psychopharmacology 111, 69–77 (1993). https://doi.org/10.1007/BF02257409

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