Alcohol responsiveness, hyperreactivity, and motor restlessness in an animal model for attention-deficit hyperactivity disorder

Abstract 

Rationale: Attention-deficit hyperactivity disorder and related pervasive developmental disorders constitute risk factors for adult alcohol abuse and antisocial behaviours, including violent offending. Objectives: The present study assessed alcohol responsiveness and hyperemotionality in neonatally 6-OHDA-treated rats, which provides an animal model for attention-deficit hyperactivity disorder. Method: Male Wistar rats were given intracerebroventricular 6-OHDA (100 µg/5 µl) or vehicle (saline-ascorbic acid) on postnatal day 3. In adulthood, we measured motor activity, defensive behaviours and ethanol responsiveness. Results: 6-OHDA resulted in depletions of brain catecholamine levels. The experimental animals were markedly hyperactive, showed increases in active defensive behaviours (fleeing) and decreases in passive defensive responses (freezing) in response to an sudden auditory signal. In tests for reactivity to the experimenter (i.e. defensiveness to innocuous stimuli), 6-OHDA rats were hyperreactive in comparison to controls. With regard to home cage 6% ethanol and water consumption, there were no differences between experimental and control rats. However, 6-OHDA rats displayed a remarkable resistance to the motor-impairing effect of alcohol (0.5–1.0 g/kg, IP). A similar hyposensitivity to the motor-suppressive effect of diazepam (5.0 mg/kg, IP) was also found. Conclusions: The present results show that adult rats exposed to 6-OHDA as neonates are motorically restless, unusually prone to respond defensively to innocuous stimuli, and considerably less sensitive to the intoxicating effects of ethanol and diazepam.