Reduced metabolic response of the aged rat brain to haloperidol

Local cerebral glucose utilization (LCGU) was determined in 49 brain regions of 3-, 12-, 24-, and 33-month-old awake Fischer-344 rats, at 30 to 120 min after administration of the dopaminergic antagonist haloperidol (HAL) at 1 mg/kg (i.p.). The quantitative autoradiographic [14C]-2-deoxyglucose technique was employed. In 3-month rats, HAL produced statistically significant (p less than 0.05) reductions in LCGU in 63% of the brain regions examined, including those having dopaminergic as well as non-dopaminergic function. With increasing age, LCGU was progressively less affected by HAL. Significant declines in LCGU occurred in 21 to 23% of the observed regions in 12- and 24-month rats, and in 10% of the 49 regions in 33-month-old rats. The peak effects of HAL on LCGU occurred later in the 33-month- than in the 3-month-old rats (90 and 60 min after HAL, respectively). The behavioral effect (catalepsy) of HAL was less in old than in young rats. Age-related differences in the cerebral metabolic and behavioral responsivities of rats to HAL are not due to differences in brain concentrations of HAL, as higher concentrations are obtained in older animals (Kapetanovic, I.M., D.J. Sweeney, and S.I. Rapoport (1982) J. Pharmacol. Exp. Ther. 221: 434-438). The differences correlate with known age-dependent structural and biochemical deficits of the central dopaminergic system and indicate reduced functioning of that system in the rat brain after 12 months of age.