Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?

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Abstract
Dopaminergic projections to the medial prefrontal cortex have been implicated in cocaine reinforcement; therefore, it was of interest to examine the locomotor effects of acute administration of cocaine to this area. Circling behavior was assessed following injections of 1.0 microliter of cocaine in doses of 0 (0.9% saline), 25, 50, and 100 micrograms/microliters into the medial prefrontal cortex of rats prepared with chronic unilateral guide cannulae. Animals were scored during four 5 min intervals of a 60 min test session that began with the central injection and placement in a flat circular arena. Cocaine was found to produce dose-dependent contraversive circling, an effect previously seen with the dopamine (DA) agonists LY 14 1865 and (+)- amphetamine, suggesting a unilateral stimulant effect. However, since cocaine has potent local anesthetic properties that have been reported to produce behavioral effects and also to inhibit the reuptake of norepinephrine and 5-HT, it was important to demonstrate that the directional bias was a dopaminergic effect. Intra-frontocortical microinjections of the local anesthetic procaine (10, 100, and 1000 micrograms in 0.5 microliter) did not induce circling. Sulpiride (0.001–10.0 micrograms in 0.5 microliter), a DA antagonist specific for the D- 2 receptors, produced ipsiversive circling in a dose-dependent manner in rats treated with (+)-amphetamine (1.5 mg/kg, i.p.). In addition, sulpiride (1.0 micrograms in 0.5 microliter) blocked the circling behavior induced by cocaine (50 micrograms in 0.5 microliter) when administered into the medial prefrontal cortex 15 min prior to the cocaine injection. These results provide further evidence for an excitatory influence of mesocortical DA on motor control.

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