The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines

Abstract

Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior through their effects on DA neurotransmission. This review focuses on how alterations in dopaminergic neurotransmission within distinct basal ganglia pathways can modify their functional output to predict and explain the acute and long term behavioral consequences of amphetamine exposure.

Figure 1

A. Schematic representation of the major pathways of the BG. Rectangular boxes denote basal ganglia structures and oval shapes denote brain structures related to the BG. B. Schematic representation of amphetamine induced changes in neurotransmission in the BG. Wide arrows represent increased activity, and dotted arrow indicate decreased activity in the pathway.

Figure 2

Model of amphetamine influence on BG and its related structures resulting in differential functional output. Amphetamines can affect specific components of the BG and other structures closely associated with the BG to mediate behavioral outcomes associated with drug use. The bold print denotes increased involvement of these structures in the behavioral outcome.