Abstract
Pigeons were trained to discriminate intramuscular injections of 5.6 mg/kg BMY 14802, a drug that has relatively high affinity forsigma binding sites, from saline in a two-key operant procedure. Many compounds that displace sigma binding failed to produce BMY 14802-like discriminative stimulus effects; these included (+)-SKF 10,047, (+)3-PPP, DTG and MR 2035; the typical antipsychotic haloperidol; the putative antipsychotics tiospirone, cinuperone and rimcazole; and the uncompetitive NMDA antagonist phencyclidine. In addition, MR 2035 and tiosperone failed to antagonize the discriminative stimulus effects of BMY 14802. The selective D2 antagonist eticlopride and the norepinephrine uptake blocker and antidepressant desmethylimipramine also failed to evoke substantial BMY 14802-appropriate responding. In contrast tosigma ligands and other reference compounds, the 5-HT1A agonists buspirone, 8-OH-DPAT and spiroxatrine dose-dependently produced BMY 14802-like discriminative stimulus effects. The limited-efficacy 5-hydroxytryptamine (HT)1Aagonist NAN 190 did not produce BMY 14802-like discriminative effects; however, it did competitively antagonize the stimulus effects of BMY 14802 and the BMY 14802-like stimulus effects of (±)-8-hydroxy-2-(di-n-propylamino)tetralin. Other serotonergic compounds failed to produce substantial BMY 14802-appropriate responding; such as 5-HT1 agonist l-5-HTP; 5-HT1A/1B agonist RU24969; 5-HT1B/1C agonistm-CPP; 5-HT1C/2 agonist quipazine; 5-HT1C/2 antagonists, metergoline and the atypical antipsychotic clozapine; and 5-HT3 antagonist ondansetron. Also, metergoline, ondansetron and pirenpirone failed to antagonize the stimulus effects of BMY 14802. These results indicate that the discriminative stimulus effects of BMY 14802 are serotonergically mediated primarily by 5-HT1A receptors rather than bysigma sites.
Footnotes
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Send reprint requests to: Dr. Susan A. Vanecek, Department of Psychiatry and Behavioral Sciences, University of Oklahoma, Health Sciences Center, P.O. Box 26901, Research Building 302-R, Oklahoma City, OK 73190-3000. E-mail: svanecek{at}etowaha.uhsc.edu
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↵1 This work was supported by United States Public Health Service Grant DA05325.
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↵2 Present address: Department of Psychiatry and Behavioral Sciences, University of Oklahoma, Health Sciences Center, P.O. Box 26901, Research Building 302-R, Oklahoma City, OK 73190-3000.
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↵3 Present address: Department of Psychology, Tobin Hall, University of Massachusetts at Amherst, Amherst, MA 01003.
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↵4 Present address: Pharmacia & Upjohn, 7000 Portage Road, Kalamazoo, MI 49001-0199.
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↵5 J. H. Woods, unpublished observations.
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↵6 E. Weber, personal communication.
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↵7 D. P. Taylor and S. H. Behling, unpublished observations.
- Abbreviations:
- BMY 14802
- α-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol
- m-CPP
- l-(m-chlorophenyl)piperazine
- DTG
- 1,3-di(2-tolyl)guanidine
- 5-HT
- 5-hydroxytryptamine (serotonin)
- l-5-HTP
- l-5-hydroxytryptophane
- MR2035
- (+)-(1S,5S,9S,2"R)-5,9-dimethyl-2′-hydroxy-2-tetrahydro-furfuryl-6,7-benzomorphanl-tartrate
- 8-OH-DPAT
- (±)-8-hydroxy-2-(di-n-propylamino)tetralin
- (+)-SKF 10
- 047, (+)-N-allylnormetazocine
- (+)-3-PPP
- (+)3-(3-hydroxyphenyl)-N,n-propyl piperidine
- NAN 190
- 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
- NMDA
- N-methyl-d-aspartate
- RU24969
- 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate
- PCP
- phencyclidine
- DTG
- ditolylguanidine
- FR
- fixed ratio
- CL
- confidence limits
- Received May 19, 1997.
- Accepted August 25, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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