| || |
|Title:||PRE-EXISTING DIFFERENCES IN THE MESOCORTICOLIMBIC DOPAMINE SYSTEM AND HPA-AXIS OF PERIADOLESCENT HIGH- AND LOW-LG OFFSPRING MAY CONTRIBUTE TO THE LOCOMOTOR RESPONSE TO AMPHETAMINE.|
| || |
|Authors/Affiliations:||2 Amanda Pomarenski*; 1 Shakti Sharma; 2 Michael Meaney; 2 Alain Gratton; |
1 Douglas Mental Health University Institute; 2 Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
| || |
|Content:||Objectives: Natural variations in maternal care have long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis and mesocorticolimbic dopamine (DA) responses to stress in adult rats. These systems also mediate the effects of psychostimulant drugs. Although enduring differences in these systems have been found in adults, relatively less is known of how maternal care affects these systems during periadolescence, a critical period during which individuals are more vulnerable to certain drug effects. Male periadolescent offspring of high- and low-licking/ grooming (LG) dams previously exposed to novelty-stress respond differently to a subsequent amphetamine (AMPH) injection. Specifically, low-LG periadolescents exhibit increased locomotor activity following an acute AMPH treatment compared to their high-LG counterparts. Given that this difference appears after only a single injection, it was hypothesized that increased AMPH-induced locomotion in low-LG periadolescent offspring may be due to pre-existing differences in the mesocorticolimbic DA system and the HPA axis. The purpose of this study was to examine potential differences in these systems in na´ve periadolescent high- and low-LG offspring.|
Materials and Methods: In the first experiment, autoradiography was used to quantify levels of D1 and D2 receptors and the DA transporter (DAT) in the VTA, NAc, CPu, SN, and PFC of na´ve male high- and low-LG offspring, which were sacrificed at PND 35 or PND 90. In the second experiment, stress recovery was examined in periadolescent high- and low-LG offspring. At PND 35, na´ve male high- and low-LG offspring were subject to 20 min restraint stress. Trunk blood was collected before, immediately after, 20, 40, and 70 min post-stress. Plasma CORT, ACTH, CBG, and testosterone at each time-point were examined using radioimmunoassays.
Results: Autoradiographic analyses revealed significantly higher levels of D1 receptor binding in the SN of periadolescent low-LG rats than in their high-LG counterparts; a trend for higher D1 receptor binding was also found in the VTA and PFC. Taken together, the density of D1 receptor binding seen in the CPu and SN of periadolescents was greater than in adult animals. Effects of maternal care were also seen in the HPA status of periadolescent animals. Low-LG animals had higher basal plasma CORT levels than high-LG offspring. While the CORT stress recovery time course of the two groups did not differ, significantly greater stress-induced increases in plasma ACTH were seen in low-LG offspring compared to their high-LG counterparts. Further, low-LG rats had higher overall levels of plasma testosterone compared to high-LG periadolescents.
Conclusion: These results indicate that naturally occurring variations in maternal care can alter prepubertal development of two key systems involved in the behavioral effects of stimulant drugs. That such alterations occur prior to adolescence, a period characterized by a greater propensity for risk-taking as well as increased exposure to novel and stressful experiences, may confer in some individuals increased vulnerability to addictive properties of stimulant drugs.
| || |