No abstract

The subthalamic nucleus (STN) is traditionally thought of as part of a system involved in motor control but recent evidence suggests that it may also play a role in other psychological processes. Here we examined the effects of STN lesions on two measures of impulsivity and found that STN lesions increased 'impulsive action' (produced behavioral disinhibition), as measured by performance on a differential reinforcement of low rates of responding task, but decreased 'impulsive choice' (impulsive decision making), as measured by a delay discounting task. In addition, amphetamine and food restriction increased 'impulsive action' and decreased 'impulsive choice' to a greater extent in STN-lesioned animals than in sham controls. We speculate that these apparently discrepant effects may be because STN lesions enhance the incentive salience assigned to rewards. These findings suggest that the STN may serve as a novel target for the treatment of psychological disorders characterized by deficits in behavioral control, such as drug addiction and attention deficit hyperactivity disorder.

No abstract

In the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so-called 'direct pathway'. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c-fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c-fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c-fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug-induced neuroplasticity.

Repeated exposure to psychostimulant drugs produces long-lasting changes in dendritic structure, presumably reflecting a reorganization in patterns of synaptic connectivity, in brain regions that mediate the psychomotor activating and incentive motivational effects of these drugs, including the nucleus accumbens and prefrontal cortex. However, repeated exposure to psychostimulant drugs also facilitates a transition in the control of some behaviors from action-outcome associations to behavior controlled by stimulus-response (S-R) habits. This latter effect is thought to be due to increasing engagement and control over behavior by the dorsolateral (but not dorsomedial) striatum. We hypothesized therefore that repeated exposure to methamphetamine would differentially alter the density of dendritic spines on medium spiny neurons (MSNs) in the dorsolateral vs. dorsomedial striatum. Rats were treated with repeated injections of methamphetamine, and 3 months later dendrites were visualized using Sindbis virus-mediated green fluorescent protein (GFP) expression in vivo. We report that prior exposure to methamphetamine produced a significant increase in mushroom and thin spines on MSNs in the dorsolateral striatum, but a significant decrease in mushroom spines in the dorsomedial striatum. This may be due to changes in the glutamatergic innervation of these two subregions of the dorsal striatum. Thus, we speculate that exposure to psychostimulant drugs may facilitate the development of S-R habits because this reorganizes patterns of synaptic connectivity in the dorsal striatum in a way that increases control over behavior by the dorsolateral striatum.