Neuroethological assessment of amphetamine-induced behavioral changes and their reversal by neuroleptics: focus on the amygdala and nucleus accumbens.

1. An ethological approach was combined with intracerebral infusions of amphetamine to broaden understanding of how this drug acts on mesolimbic neuronal systems to alter behavior. 2. Rats, tested in sets of three, were allowed to interact with each other or with various novel objects in an open-field arena. Specific behavioral responses were assessed and grouped into several broad categories: motivation (movement directed toward novel objects), social (movement involving contact with other rats), and motor (movement without obvious direction toward environmental stimuli) as well as no movement (quiet rest). 3. Infusion of d-amphetamine (10 micrograms/microliter) into either the amygdala or nucleus accumbens elevated motor behavior relative to control rats in the set, but only amygdaloid infusions also increased the motivation score. Intra-amygdaloid clozapine or haloperidol blocked the increase in this score, but only clozapine also blocked the motor effects of intra-amygdaloid amphetamine. 4. Although neither neuroleptic in the accumbens blocked the amphetamine-induced increase in the motor category, both clozapine and haloperidol lowered the motivation score below the amphetamine level. 5. The results suggest a role for the amygdala in the motivational component of amphetamine-induced behavioral effects. Both neuroleptics, moreover, appear to reverse this component perhaps by acting via either amygdaloid or accumbal mechanisms. Although follow-up studies are warranted, a neuroethological approach is likely to shed new light on the neuronal systems underlying the complex behavioral changes induced by amphetamine and related stimulants.