Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia.

The acquisition of behavioral inhibition of 6 rats that recovered from the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (mPFC) was compared with that of 5 control rats (sham). Differential reinforcement of low rates (DRL) schedules of reinforcement of 5, 10, 20, and 30 s estimated the inhibition of responding to obtain the arranged reinforces. For both groups of rats, responses decreased as a function of number of sessions, with slopes of regression lines showing a negative correlation. The number of obtained reinforcers increased with consecutive sessions of the same DRL. A nonlinear hyperbolic model fitted these data well, accounting for most of the variability that occurred as a function of number sessions. Both groups showed a positive correlation between obtained and arranged reinforcers (Pearson's r ϭ .999), with lines of best fit showing slopes close to 1.0. Distributions of interresponse times (IRTs) were used to estimate probabilities of IRTs smaller than DRL values. A 4-parameters logistic (4PL) nonlinear regression model fitted these data well, estimating the initial probability to emit short IRTs, inflections points, sensitivity to changes in IRTs, and maximum asymptote. Our findings allowed to conclude that despite 6-OHDA lesions extended training in the DRL schedule results in learning, and that a 4PL model describes well the performance of rats responding to DRL schedules of different values.