Cortical and Dopaminergic Regulation of Amphetamine-Induced Changes In Striatal Single-Unit Activity in Awake, Behaving Rats

Abstract

The striatum and its dopaminergic input from the ventral midbrain are known to play a critical role in the behavioral effects of amphetamine and related psychomotor stimulants. Relatively little information is available, however, on the neuronal mechanisms underlying these behavioral effects. In an initial attempt to address this issue, a series of single-unit recording experiments has been carried out in the striatum of awake, behaving animals. Early data obtained from cats revealed a tendency for amphetamine to accelerate striatal neuronal activity in parallel with the drug-induced behavioral activation (Trulson and Jacobs, 1979). Consistent with these findings, West et al. (1987) reported that amphetamine increased unit activity in virtually all striatal neurons sampled from rats trained to walk on a treadmill. In contrast, other investigators found both excitatory and inhibitory striatal responses to amphetamine in freely moving rats (Gardiner et al., 1988; Ryan et al., 1989). Subsequent research has shown that striatal neurons firing in close temporal association with movement are significantly more likely to increase activity in response to amphetamine than neurons in which neuronal activity is unrelated to movement (Haracz et al, 1989; Rebec et al., 1991). In fact, nonmotor-related neurons typically are inhibited by the drug. Although these changes in unit activity may occur secondarily to an amphetamine–induced behavioral change, data obtained from behavioral clamping techniques, which attempt to control for behavioral feedback effects by comparing neuronal activity during matched pre- and post-amphetamine behaviors, argue against this view (Haracz et al., 1993). In fact, direct infusions of amphetamine into the striatum of freely moving animals activates motor- and inhibits nonmotor-related neurons several minutes prior to the onset of overt behavioral changes (Wang and Rebec, 1992). Thus, amphetamine-induced changes in striatal activity appear to reflect a direct action of this drug on striatal neurons rather than a secondary response associated with behavioral activation. By creating a divergence in firing rate between motor-and nonmotor-related neurons, amphetamine may help to bias the striatum toward expression of the drug–induced behavioral response. In the present series of experiments, we focused on some likely mechanisms by which dopamine may regulate the changes in striatal neuronal activity produced by amphetamine.