CART peptide in the nucleus accumbens regulates psychostimulants: Correlations between psychostimulant and CART peptide effects

Abstract

In this study, we reexamined the effect of CART peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis.

CART Peptide Regulates Psychostimulant-Induced Activity and Exhibits a Rate Dependency

“…But, it was also found that injection of CART peptide tended to stimulate or increase the activity of animals who did not respond to PSs (Figure 1). This finding reinforced our earlier hypothesis that CART peptides in the NAc regulate the action of PSs and dopamine [2,10]; when the PS effect on LMA was a significant increase, CART peptide inhibited the LMA, and conversely, when PS had little or no effect on LMA, CART peptide stimulated LMA. Thus, CART peptide seems to act to maintain PS-induced LMA within a certain window of activity.…”

“…In summary, a new analysis of data on the effects of CART peptide on cocaine-induced LMA [10] supports the previous hypothesis that CART regulates the effects of PSs, and also shows that CART peptide exhibits a rate dependency.…”

“…The experiments were carried out as described by Job and Kuhar [10]. The left or y -axis is the “CART peptide effect” which is determined as the difference between (1) the cocaine-induced LMA with CART peptide and (2) the cocaine-induced LMA without CART peptide.…”

“…Thus the CART peptide effect shows a rate dependence on cocaine-induced LMA. The figure shown is Figure 2(c), females, reproduced from Job and Kuhar [10], with permission.…”

“…While previous studies have focused on the average effect of CART peptide in groups of animals, a recent study from our laboratory examined the effect of the peptide on the action of PSs in each individual animal [10]. This approach gives more visibility to those animals that were not always stimulated by PSs, presumably because of the state of the animal.…”