Evidence for separate neural mechanisms for the timing of discrete and sustained responses

Methamphetamine (MAP), an indirect dopamine agonist, has been shown to produce a leftward shift in the time of responding under operant response protocols that encourage repetitive responding (e.g., lever pressing). Given the involvement of striatal dopamine activity in the control of discrete motor behavior, as well as in the timing of these responses, an important question arises as to whether a dissociation is possible between changes in the timing of discrete responding and timing of other behaviors. Rats were trained on a modified peak-interval (PI) procedure such that reward was contingent upon the presence of the animal's snout in a nosepoke apparatus at the target time, as an alternative to the typical requirement of a discrete head entry response. Thus spatial selection, but not necessarily motor behavior, at the appropriate time was required to receive a reward. Rats were given MAP in one of 3 doses (0.5, 1.0, or 1.5 mg/kg), or a saline control injection before PI sessions to determine whether the drug elicits a dose-dependent effect on timing of spatial position, as it has been shown to do for discrete behaviors. Following administration of MAP, the peak time of the proportion of time spent in the nosepoke did not change, while the peak time of the rate of response shifted to the left. Single-trial analysis revealed a similar pattern: Position of response step functions defined by being in the nosepoke did not shift, but step functions based on response rate changed with increasing doses of MAP. These data support a model of multiple timing processes controlling different behaviors, at least one of which is specific to discrete motor behavior and is modifiable by dopamine.