Morehead State University
Non-Dopaminergic Influence on the Mesolimbic Dopamine System
Institution
Morehead State University
Faculty Advisor/ Mentor
Ilsun White
Abstract
The mesolimbic dopamine system, which consists of the nucleus accumbens (NAc), prefrontal cortex, and ventral tegmental, mediates a wide-range of behavior, simple to complex. Increasing evidence indicates that other limbic structures (nondopaminergic), such as hippocampus (HIP) and amygdala (AMg), may modulate behavior mediated by the mesolimbic dopamine system. The present study investigated the involvement of HIP and AMg in amphetamine-induced hyperactivity. Previously, we reported that excitatory input from HIP to NAc is critical for expression of hyperactivity. Other studies indicate that AMg may provide inhibitory modulation. Thus, we hypothesized that HIP and AMg would exert opposing roles and that either excitation of HIP or inhibition of AMg would augment amphetamineinduced hyperactivity. Wistar rats were lesioned (NMDA or sham) in either HIP or AMg. After recovery, the rats’ activity was monitored in an open-field before and after amphetamine (1mg/kg, i.p.). Activity was measured by distance traveled at 5 minutes intervals for 60 minutes. Following amphetamine, HIP-lesioned rats showed decreased activity, whereas AMg-lesioned rats showed increased hyperactivity, compared to the shams. Our data provides evidence that HIP and AMg, are critical in influencing the expression of amphetamine-induced behavior, and supports the hypothesis that HIP and AMg provide opposing influence on expression of hyperactivity following systemic amphetamine. Future research on the precise roles of these structures will enhance our understanding of the way addictive drugs influence the mesolimbic system to produce changes in behavior.
Non-Dopaminergic Influence on the Mesolimbic Dopamine System
The mesolimbic dopamine system, which consists of the nucleus accumbens (NAc), prefrontal cortex, and ventral tegmental, mediates a wide-range of behavior, simple to complex. Increasing evidence indicates that other limbic structures (nondopaminergic), such as hippocampus (HIP) and amygdala (AMg), may modulate behavior mediated by the mesolimbic dopamine system. The present study investigated the involvement of HIP and AMg in amphetamine-induced hyperactivity. Previously, we reported that excitatory input from HIP to NAc is critical for expression of hyperactivity. Other studies indicate that AMg may provide inhibitory modulation. Thus, we hypothesized that HIP and AMg would exert opposing roles and that either excitation of HIP or inhibition of AMg would augment amphetamineinduced hyperactivity. Wistar rats were lesioned (NMDA or sham) in either HIP or AMg. After recovery, the rats’ activity was monitored in an open-field before and after amphetamine (1mg/kg, i.p.). Activity was measured by distance traveled at 5 minutes intervals for 60 minutes. Following amphetamine, HIP-lesioned rats showed decreased activity, whereas AMg-lesioned rats showed increased hyperactivity, compared to the shams. Our data provides evidence that HIP and AMg, are critical in influencing the expression of amphetamine-induced behavior, and supports the hypothesis that HIP and AMg provide opposing influence on expression of hyperactivity following systemic amphetamine. Future research on the precise roles of these structures will enhance our understanding of the way addictive drugs influence the mesolimbic system to produce changes in behavior.