The effects of l- and d-baclofen were studied on two dopamine-dependent behaviours in rats, namely the hyperactivity response after bilateral injection of 12 μg dopamine into the nucleus accumbens and the state of catalepsy produced after an intraperitoneal injection of 0.6 mg/kg of the neuroleptic fluphenazine. Both l- and d-baclofen (0.5-50 μg) injected bilaterally into the nucleus accumbens septi 60 min after the bilateral injection of dopamine strongly antagonized hyperactivity in a dose-dependent manner. Significance was achieved for both isomers at 5, 10 and 50 μg doses. This effect was rapid in onset and lasted longer than 2 hr. Both l- and d-baclofen produced a highly significant potentiation of fluphenazine's ability to produce catalepsy at 10 mg/kg and 25 mg/kg, the effect of d-baclofen was also significant at 5 mg/kg. In a further experiment the effect of dl-, d- and l-baclofen on motor co-ordination was tested with animals on a rotarod. Whilst d-baclofen had no effect in this system, l-baclofen severely impaired the performance at all doses above 5 mg/kg. In all experiments animals receiving d-baclofen showed no perceptible loss in muscle tone. Animals receiving l-baclofen displayed great reduction in muscle tone with marked sedation and analgesia. Such muscle hypotonia and sedation would explain the effect of l-baclofen in both the motor coordination and dopamine-dependent behaviours. The effect of d-baclofen would however be apparently more specific to an interaction with cerebral dopamine systems. © 1979.
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