GABA and dopamine interaction in the basal ganglia: dopaminergic supersensitivity following chronic elevation of brain gamma-aminobutyric acid levels.
The influence of chronic activation of the gamma-aminobutyric acid (GABA) system on dopaminergic function was evaluated in male rats. Activation of the GABA system was achieved by raising the brain concentration of GABA with aminooxyacetic acid (AOAA), a GABA-transaminase (GABA-T) inhibitor. Repeated i.p. injection (40 or 80 mg/kg/day for 8 days) of AOAA produced a sustained elevation of GABA concentration in the striatum. Beginning 26 h following the last dose of a regimen of AOAA treatment (80 mg/kg/day for 8 days), the animals exhibited a characteristic spontaneous 'sham-fighting' behavioral stereotypy which peaked at 34 h after the last dose of AOAA; this spontaneous behavior dissipated by 38 h postdose. When challenged with apomorphine, the sham-fighting behavior was interspersed with intense fighting episodes; these precipitated behaviors were evident for up to 2 weeks posttreatment observation period. Animals given a lower dose of AOAA (40 mg/kg/day X 8) did not show signs of spontaneous sham-fighting, but responded with fighting upon apomorphine challenge. Qualitatively similar behavioral effects were obtained when gamma-acetylenic GABA (30 mg/kg/day, i.p. for 8 days) was used as the inhibitor of GABA-T. Measurement of dopamine and its acid metabolites in the striatum showed an enhanced turnover of dopamine during the spontaneous behavioral response, suggesting a rebound phenomenon. The levels of 5-hydroxytryptamine or its acid metabolite or neuroactive amino acids such as glutamate, aspartate, taurine, glycine, glutamine in the striatum were not altered by any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
D000596:Amino Acids / Q000378:metabolism; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004351:Drug Resistance; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D000625:Aminooxyacetic Acid; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine