Responses of neurons in dorsal striatum during amphetamine-induced focused stereotypy

The phase of highly focused, repetitive behavior (stereotypy) induced by amphetamine in rats emerges after an initial period of locomotor activation. To assess the neuronal correlates of this behavioral transition, single-unit activity was recorded from the dorsal striatum of awake, unrestrained rats. Units were first characterized in terms of their responsiveness to spontaneous movement. Various types of motor-related neurons were identified. Some increased activity above resting baseline during specific movements such as forward locomotion or turning of the head, while others were excited during periods of general behavioral activation. Neurons that showed no consistent change in firing rate during overt movement were classified separately. Administration of 5.0 mg/kg d-amphetamine caused a steady increase in the overall neuronal response through both the locomotor and stereotypy phases. An analysis of specific neuronal types, however, revealed distinct, phase-related shifts in firing rate. Locomotor-related neurons discharged rapidly during the early phase of the amphetamine response and then declined toward baseline as focused stereotypy emerged. Cells found to be excited primarily during head movements showed relatively small changes shortly after drug administration but increased markedly in conjunction with intense head-movement activity associated with focused stereotypy. Other neurons, which increased activity nonselectively to a wide range of movements, showed progressive increases in firing rate during both behavioral phases elicited by the drug. Subsequent administration of 1.0 mg/kg haloperidol typically reversed the neuronal changes and blocked amphetamine-induced focused stereotypy. Nonmotor-related cells responded inconsistently to amphetamine, showing an inhibition, excitation, or no change in rate. Previous assessments of neuron-behavior relationships have shown that changes in motor-related neuronal activity are not secondary to amphetamine-induced behavioral changes, though this finding may not apply in all cases. At doses capable of eliciting focused stereotypy, therefore, amphetamine appears to trigger a complex pattern of striatal activity that governs the behavioral response. This conclusion supports steadily increasing evidence that the role of striatal neurons in amphetamine-induced focused stereotypy is shaped by multiple synaptic mechanisms.