Differential effects of intrafrontocortical microinjections of dopamine agonists and antagonists on circling behavior of rats

Asymmetric posturing and circling behavior resulting from acute unilateral manipulation of central dopamine have been used to assess this neurotransmitter's contribution to motor control. Although providing extensive evidence for the involvement of mesolimbic and nigrostriatal dopamine in motor activity, this approach has not been used to study the mesocortical system. We now report circling behaviour following acute manipulation of frontal cortical dopamine. Unilateral microinjections of the agonists, (+)-amphetamine (12 and 25 micrograms in 1.0 microliter) and LY 141865 (12 micrograms in 1.0 microliter) resulted in contraversive circling. Conversely, unilateral intrafrontocortical microinjections of the antagonist, metoclopramide (25 and 100 micrograms in 1.0 microliter) resulted in ipsiversive circling in amphetamine (1.5 mg/kg, i.p.) pretreated rats. Lower central doses of each drug and vehicle injections had no significant effect. These results provide evidence for an excitatory influence of mesocortical dopamine on motor control. This finding may implicate frontal cortical dopamine in the extrapyramidal motoric side effects of chronic neuroleptic treatment which previously have been attributed to dopamine function in subcortical areas.