Effects of maturation and aging on behavioral responses to haloperidol in the rat

Male Sprague-Dawley rats were evaluated between ages 18 and 825 days for responses to doses of haloperidol (0 and 0.05-10 mg/kg, IP). Catalepsy, ptosis, and inhibition of general motor activity showed steady decreases in sensitivity to the drug with age during the first 1.5 years of maturation, while rats older than 1.5 years had strikingly increased sensitivity to the activity-inhibiting and cataleptic effects of the drug. The efficacy of haloperidol on all tests in 110-day old rats was indistinguishable whether food was available continuously, or restricted to reduce body weight by 55%, indicating that the effects of maturation are due to aging and not to increasing body weight. The effects may be due to altered drug metabolism or altered sensitivity of the central nervous system to neuroleptic agents. Clinical impressions too, indicate that immature and elderly patients are more sensitive to these and other psychotropic drugs than are young adults.