Effects of aminooxyacetic acid and baclofen on catalepsy, striatal homovanillic acid increase and antinociception caused by methadone in rats.

The effects of aminooxyacetic acid (AOAA) and baclofen on the catalepsy, striatal homovanillic acid (HVA) increase and antinociception caused by methadone were studied in rats. Antinociceptive responses were tested by the electric foot-shock method. A new type of stimulator unit which delivered nearly constant current over a wide range of output voltage and which was noiseless was designed and its construction is described. AOAA (25 mg/kg) which increases the cerebral concentration of gamma-aminobutyric acid (GABA) and baclofen (10 mg/kg), a structural analogue of GABA, did not change the catalepsy induced by methadone (5 mg/kg). AOAA (25 and 50 mg/kg) alone did not alter the striatal HVA content and had no effect on the methadone induced HVA increase. Baclofen (10 mg/kg) increased the striatal HVA content by 19% (P less than 0.01) and reduced the methadone-induced HVA increase by 36% (P less than 0.01). AOAA (25 mg/kg). These results suggest that narcotic analgesics might cause catalepsy and increase striatal dopamine turnover by some other mechanism than neuroleptics. The results support the suggestion that GABA might be involved in pain mechanisms.