6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure.

Abstract

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.

Behavioral inhibition in rats after 6-hydroxydopamine lesions of the medial prefrontal cortex.

“…In terms of the history of reinforcement of the rats used in the present study, the same rats were also used in our previous study (Elcoro et al, 2014) in which measures of timing (e.g., peak times) were unaltered after the lesions while overall responding was diminished. This overall decrease in responding was especially marked early after the lesions; with more sessions, partial recovery occurred, not to the extent achieved by the sham group (i.e., back to their prelesion baseline).…”

“…Acquisition of responding in a PIP as the one used by Elcoro et al (2014) involves eventual decrease in responding (Kaiser, 2008(Kaiser, , 2009 during peak trials given that there is repeated experience with periods of extinction. This pattern of decreased responding during peak trials within the history of reinforcement of the rats may have provided an advantage to performing in a DRL procedure evaluated in the present study.…”

“…Accordingly, the present study of has a twofold objective: to (a) show that six months after the lesions of the mPFC caused by bilateral 6-OHDA, rats learn to inhibit responses postponing arranged reinforcers by DRL schedules of 5, 10, 20, and 30 s; and (b) demonstrate that a 4-parameters logistic (4PL) nonlinear regression model fits well data of DRL schedules, estimating the initial probability to emit short IRTs, inflections points, sensitivity to changes in IRTs, and maximum asymptote as follows: where A 1 is the minimum asymptote or initial value (probability here), p is the power or slope of the curve, x 0 the inflection point (point in the curve where the curvature changes direction), and A 2 the maximum asymptote or final value. Relative to our previous study (Elcoro, Thompson, Kelly, Pegan, & Aparicio, 2014), the contribution of the present study is to provide a detailed analysis of the acquisition of behavioral inhibition showing that extended training in the DRL schedule results in learning despite the lesions.…”

“…Relative to our previous study (Elcoro, Thompson, Kelly, Pegan, & Aparicio, 2014), the contribution of the present study is to provide a detailed analysis of the acquisition of behavioral inhibition showing that extended training in the DRL schedule results in learning despite the lesions.…”

The Peak Interval Procedure in Rodents: A Tool for Studying the Neurobiological Basis of Interval Timing and Its Alterations in Models of Human Disease

“…Olton (1989) and Olton et al (1988) observed a later peak. More recently, Elcoro et al (2014) showed that 6-Hydroxydopamine lesions of medial prefrontal cortex led to flatter response distributions, suggesting lower precision.…”