Benzodiazepine receptor mediated discriminative cues: Effects of GABA-ergic drugs and inverse agonists
| Autor: | Erik B. Nielsen, Alice M. Holohean, James B. Appel, James D. Valentine |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
Male
Agonist medicine.drug_class Receptors Cell Surface Pharmacology FG-7142 General Biochemistry Genetics and Molecular Biology Chlordiazepoxide Discrimination Learning chemistry.chemical_compound DMCM medicine Animals Inverse agonist General Pharmacology Toxicology and Pharmaceutics Benzodiazepine Diazepam Rats Inbred Strains Isoxazoles General Medicine Receptors GABA-A Receptor antagonist Rats chemistry Cues medicine.drug |
| Zdroj: | Life Sciences. 33:2213-2220 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(83)90293-x |
| Popis: | Rats were exposed to a two-layer drug discrimination procedure using the benzodiazepine (BZ) receptor inverse agonists N′-methyl-β-carboline-3-carboxamide (FG 7142) or methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM). FG 7142 (30 mg/kg) failed to acquire discriminative stimulus control, although it did suppress responding. The same group of animals was trained successfully to discriminate diazepam (DZP, 2.5 mg/kg) from vehicle. The DZP cue was potentiated by the GABA agonist 4,5,6,7-tetrahydro-isoxazolo [5, 4-c] pyridin-3-ol (THIP, 1–3 mg/kg); THIP alone produced vehicle-appropriate responding. In addition, clonazepam (0.2 mg/kg) and chlordiazepoxide (5 mg/kg) substituted for DZP (with potencies of 7.5 and 0.25 times that of DZP, respectively). In antagonism tests, FG 7142 (5–17.5 mg/kg), methyl-β-carboline-3-carboxylate (β-CCM, 2.5 mg/kg), nicotine (0.3 mg/kg), harmaline (5 mg/kg) and naltrexone (10 mg/kg) did not effect, bicuculine (2 mg/kg) and DMCM (1 mg/kg) partially blocked, and the BZ receptor antagonist Ro 15–1788 (40 mg/kg) completely blocked the discriminative stimulus effects of DZP. In animals trained to discriminate DMCM (0.2 mg/kg) from vehicle, 95% substitution occured with bicuculline (2 mg/kg); DZP (1–5 mg/kg) completely antagonized DMCM. These results indicate that the DZP cue is mediated by GABA-coupled BZ receptors and that GABA may modulate the efficacy of a BZ at its receptor site. However, since inverse BZ receptor agonists (FG 7142, DMCM and β-CCM) were, at best, only marginally effective in antagonizing DZP, the DZP cue may be mediated by a distinct subclass of BZ receptors. |
| Databáze: | OpenAIRE |
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