Neuronal and behavioral correlates of intrastriatal infusions of amphetamine in freely moving rats.

When injected systemically in rats, amphetamine routinely activates striatal neurons that increase firing rate in close temporal association with movement but suppresses nonmotor-related neurons. To assess the role of striatal mechanisms in these opposing effects, D-amphetamine (20 micrograms/microliters) was infused (10 microliters/h) directly into the striatum of awake, behaving rats and single-unit activity was recorded simultaneously at the infusion site. Intrastriatal amphetamine reliably activated motor-related, but suppressed nonmotor-related neuronal activity shortly after infusion onset. These changes in firing rate preceded overt behavioral changes, in most cases by several minutes. When they did emerge, behavioral responses were characterized mainly by focused sniffing and head bobbing. Interestingly, the strongest behavioral responses, as measured by onset latency and response magnitude, were likely to result from infusions into motor-related rather than nonmotor-related recording sites. Systemic injection of haloperidol (1.0 mg/kg) shortly after infusion offset suppressed both behavior and striatal neuronal activity. Control infusions of intrastriatal saline had no consistent effect on either striatal neuronal activity or behavior. Collectively, these results indicate that the divergence in firing rate between motor- and nonmotor-related striatal neurons reflects an intrinsic action of amphetamine in the striatum rather than a secondary effect of behavioral feedback. Moreover, the linkage of motor-related striatal areas with the strongest behavioral responses to amphetamine suggests important functional differences between motor- and nonmotor-related striatal neurons.