Effects of gamma-amino butyric acid (GABA) and baclofen on the methylphenidate-induced behavior in rats during ontogenesis

Abstract Behavioral aspects of 20 mg/kg of IP methylphenidate (MP) were examined in Sprague-Dawley rats post-treated with GABA (10, 12.5, 15, 20 and 30 mg/kg IP) or d,l-baclofen (2.5, 10 mg/kg IP) at 8–9, 12–13 and 20–22 days after birth. Animals of the same age and body weights were transferred in pairs to Animex activity meter for motility and locomotor movements. Compared to saline controls, MP enhanced activity in all age groups. Stereotyped behavior characterized by sniffing the floor, gnawing, biting, licking and repetitive back and forth head movement was much stronger in 20–22 day rats compared to younger subjects, appearing within 5 min, and continuing for 1.0 to 1.5 hr. The 10 mg/kg dose of baclofen produced a uniform block of both MP-induced enhanced activity and stereotypies in all age groups within 15–25 min when administered 10 min following MP. Baclofen (10 mg/kg) also consistently increased rectal temperatures by 1–2.5°C in all age groups examined. GABA, on the other hand, had age dependent responses. In 12–13 day old rats, the antagonistic effect of GABA on MP stereotypies and enhanced locomotion was moderate by 10, 12.5 and 15 mg/kg and marked by 20 and 30 mg/kg doses; GABA, however, had milder effects in 8–9 day old rats and had no effects in the 20–22 day age group. Additionally, GABA produced no effect on the rectal temperature in all age groups examined. These preliminary results suggest that the MP-induced stereotypies and enhanced activity may involve central dopaminergic-GABAergic systems.