Abstract
In this study we examined the effects of 5-HT1A ligands in rats trained to discriminate 0.16 mg/kg i.p. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) from saline in a two-lever, fixed ratio (FR)10 schedule of food reinforcement, and in pigeons trained to discriminate 0.31 mg/kg i.m. 8-OH-DPAT from saline in a two-key, FR30 schedule of food reinforcement. In both species, 8-OH-DPAT and a variety of structurally unrelated 5-HT1A ligands occasioned dose-related, relatively high levels of drug-appropriate selection (i.e. ≥67%). A significant positive correlation was found between estimated ED50 values in both species (r = 0.84, P < .001). Further, 5-HT1A antagonists, NAN-190, penbutolol, (−)-pindolol, tertatolol and WAY-100635, produced dose-related decreases in 8-OH-DPAT-appropriate selection, and their potencies for antagonism in rats and pigeons were highly correlated (r = 0.96, P < .01). The potency of WAY 100635 in rats and pigeons was quantified by Schild analysis (apparent in vivopA2 values: 7.8 vs. 8.3, ratvs. pigeon, respectively). Although most 5-HT1A agonists produced similar 8-OH-DPAT-like discriminative stimulus effects in both species, two compounds, lisuride and eltoprazine, occasioned high levels of drug-appropriate selection in pigeons, but not in rats. In contrast, idazoxan, yohimbine, LEK 8804 and BMY 7378 produced greater effects in rats. Among this latter group of compounds, only BMY 7378 blocked the discriminative stimulus effects of 8-OH-DPAT in pigeons, which suggested that intermediate levels of drug-appropriate selection observed with the remaining compounds are not necessarily the result of low intrinsic activity. Overall, these results demonstrate similarities in the discriminative stimulus effects of 8-OH-DPAT in rats and pigeons despite different training conditions (e.g., training dose and route of administration). Even so, the finding that some 5-HT1A ligands did not produce similar effects in rats and pigeons illustrates the need to examine possible 8-OH-DPAT-like discriminative stimulus effects of compounds in both species.
Footnotes
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Send reprint requests to: Mark S. Kleven, Ph.D., Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres Cedex France.
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↵1 Animals were cared for in accordance with guidelines set by the U.S. Department of Health and Human Services for humane treatment of animals (Guide for the Care and Use of Laboratory Animals, U.S. DHHS, PHS, National Institutes of Health publication No. 85–23, revised 1985) and the experimental protocols [No. 002 (pigeons) and No. 009 (rats)] were carried out in accordance with French law and the local ethical committee guidelines for animal research.
- Abbreviations:
- 8-OH-DPAT
- 8-hydroxy-2-(di-n-propylamino)tetralin
- BMY 14802 (also designated BMS 110100)
- α-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol
- BMY 7378
- 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azapirol[4,5]-decane-7,9-dione
- DA
- dopamine
- DS
- discriminative stimulus
- FG5974
- (2–4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl)-3-pyridinecarboxylic acid
- FR
- fixed ratio
- LEK-8804
- 9,10-didehydro-N-(2-propynyl)-6-methylergoline-8b-carboxamide
- NAN-190
- 1-(2-methoxyphenyl)-4-[(4–2-phthalimido)butyl]piperazine
- S14506
- 1-[[-4-(fluorobenzoylamino)ethyl]-ethyl]-4-(7-methoxy-naphthyl)piperazine
- GR-127
- 935, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiozol-3-yl)[1,1-biphenyl]-4-carboxamide
- LY228729
- (−)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz-{c,d}-indole-6-carboxamide
- MDL-72832
- 8-[4-(1,4-benzodioxin-2-yl-methylamino)butyl]8-azaspiro[4,5]-decane-7,9-dione
- MDL-73005EF
- 8-[2-(1,4-benzodioxin-2-yl-methylamino)ethyl]8-azaspiro[4,5]-decane-7,9-dione
- STC
- sessions to criterion
- WY-50
- 324, N-(29(4-(2-pyrimidinyl)-1-piperazinyl)ethyl)tricyclo(3.3.1.1(3,7)) decane-1-carboxamide
- TFMPP
- N-(3-trifluoromethylphenyl)piperazine
- (S)-WAY-100135
- (+)-N-tert-butyl-3-(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenylpropanamide
- WAY-100635
- N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cy-clohexanecarboxamide
- 5-HT
- serotonin
- Received June 12, 1997.
- Accepted September 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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