Block of conditioned avoidance responding in the rat by substituted phenylpiperazines
| Autor: | Gregory E. Martin, Malcolm K. Scott, William J. Baldy, Joanne R. Mathiasen, Robert J. Elgin, James M. Kesslick, Richard P. Shank |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Male
Metergoline medicine.drug_class Catalepsy Pharmacology Piperazines Receptors Dopamine chemistry.chemical_compound In vivo Conditioning Psychological Avoidance Learning medicine Animals Binding site Behavior Animal Rats Inbred Strains medicine.disease Receptor antagonist Rats Inbred F344 Rats Amphetamine Stereotypy (non-human) Serotonin binding chemistry Receptors Serotonin Anesthesia Serotonin |
| Zdroj: | European Journal of Pharmacology. 156:223-229 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(88)90325-1 |
| Popis: | Ortho-nethoxyphenylpiperazine (OMPP) and meta-substituted chlorophenylpiperazine (MCPP) blocked conditioned avoidance responding (CAR) in the rat ((ED 50 values = 5.6 (4.6, 7.3) and 2.4 (1.9, 2.9) mg/kg i.p. (95% confidence limits), respectively) without markedly altering escape responding. Since this test predicts antipsychotic efficacy, the piperazines were examined in radioligand binding assays and found to have no affinity for dopamine (DA) binding sites, but were active at serotonin binding sites. OMPP displaced ligands for the 5-HT 1A binding site with high affinity (K i = 9.5 (5.4, 17.9) nM) but was inactive at 5-HT 2 sites (K i > 1000 nM). MCPP, on the other hand , displaced ligands for 5-HT 1 , 5-HT 1A and 5-HT 2 binding sites with similar potencies (K i values = 25 (3, 67), 23 (14, 40) and 40 (33, 48) nM, respectively). Pretreatment with metergoline (1.0 mg/kg i.p. −30 min) reduced MCPP- but not OMPP-induced block of CAR. OMPP, on the other hand, acted as a DA receptor antagonist in vivo blocking amphetamine-induced stereotyped behavior, whereas MCPP did not. Neither produced catalepsy even given in doses 8–10 times those required to block CAR. Insofar as these compounds lack antidopaminergic activity in vivo, yet are active in a test (CAR) predictive of antipsychotic activity in which DA receptor antagonists are active, they may be novel antipsychotic agents, or, perhaps, false positives in the CAR paradigm. |
| Databáze: | OpenAIRE |
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