Bilateral neurochemical changes induced by unilateral cerebral haloperidol administration: evidence for cerebral asymmetry in the rat.

Bilateral alterations in dopamine metabolism were determined in the striatum, olfactory tubercle, and frontal cortex of rats pretested for circling behavior. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high-performance liquid chromatography 15 min after right or left intracarotid infusion of haloperidol. Concentrations of DOPAC and HVA were significantly increased in the striatum and frontal cortex ipsilateral to the side of haloperidol infusion, regardless of whether it was right or left. In contrast, the concentrations of these metabolites were unchanged in the olfactory tubercle after a right side infusion, but bilateral increases were evident after a left side infusion. Higher levels of DOPAC and HVA were also apparent in the left striatum and olfactory tubercle after intravenous jugular administration of haloperidol. Dopamine levels were significantly lower in the left striatum and right olfactory tubercle after intravenous haloperidol infusions. 5-HIAA concentrations were higher in the left olfactory tubercle following left side infusions of haloperidol. These data indicate that unilateral cerebral administration of haloperidol induces asymmetric and side-dependent alterations in dopamine and serotonin metabolites. These differences appear to be due to intrinsic variations in the sensitivity to haloperidol, but are not associated with the direction of circling behavior.