| Autor: |
C R, Ashby, R, Rohatgi, J, Ngosuwan, T, Borda, M R, Gerasimov, A E, Morgan, S, Kushner, J D, Brodie, S L, Dewey |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Synapse (New York, N.Y.). 31(2) |
| ISSN: |
0887-4476 |
| Popis: |
Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-induced increases in dopamine (DA) concentrations in both the rodent and primate brain. Furthermore, it abolishes cocaine self-administration and conditioned place preference, while having no effect on locomotor activity or drug delivery to the brain. In an effort to better understand the mechanisms underlying this inhibition, we examined the effect of the selective GABA(B) receptor antagonist SCH 50911 on the GVG-induced decrease in cocaine's elevation of extracellular DA concentrations in the nucleus accumbens (NACC). Cocaine administration alone (20 mg/kg i.p.) produced a 480% increase in extracellular NACC DA levels. GVG (300 mg/kg i.p.) significantly reduced this increase by 25% (P0.01). In sharp contrast, extracellular DA levels increased to 550% after the sequential administration of SCH 50911 (3 mg/kg i.p.), GVG, and cocaine. This increase is significantly different than GVG and cocaine (P0.05) but similar to cocaine alone. These results demonstrate that the GABA(B) antagonist SCH 50911 was able to completely abolish GVG's inhibition of cocaine-induced increases in DA in the NACC and implicates the GABA(B) receptor in the mechanism underlying this inhibition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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