Behavioral disinhibition requires dopamine receptor activation

Rationale: Behavioral disinhibition is a manifestation of impulsive behavior that is prominent in the psychopathology of various psychiatric disorders, but the underlying neural mechanisms are unclear. Behavioral disinhibition can be investigated by measuring premature responding in the 5-choice serial reaction time task (5-CSRTT) in which attentional parameters can be measured as well. Objective: The objective of the study was to investigate the involvement of dopamine neurotransmission in behavioral disinhibition using the 5-CSRTT in rats. Methods: The effects of amphetamine, cocaine, nicotine, the dopamine reuptake inhibitor GBR 12909, the noradrenaline reuptake inhibitor desipramine, the dopamine D1 receptor antagonist SCH 23390, and the dopamine D2 receptor antagonist eticlopride were studied in rats that were well-trained in the 5-CSRTT. Subsequently, the effects of amphetamine, cocaine, and nicotine were tested after pretreatment with SCH 23390 or eticlopride. Results: What amphetamine, cocaine, and nicotine had in common is that they increased premature responding. However, these drugs had distinct effects on attentional parameters. GBR 12909 also enhanced premature responding, whereas desipramine reduced it. Eticlopride by itself had no effect on premature responding but it attenuated the increases in this parameter evoked by amphetamine, cocaine, or nicotine. SCH 23390 reduced premature responding on its own and also reduced its drug-induced enhancement. Conclusion: The present data show that behavioral disinhibition, i.e., the inability to withhold a premature response, is a common effect of drugs of abuse and that this effect is the result of enhanced dopaminergic neurotransmission. In addition, dopamine D1 and D2 receptors play important, but perhaps distinct roles, in inhibitory control of behavior.