Effects of selective dopamine D3 receptor partial agonist/antagonists on oxycodone self-administration and antinociception in monkeys

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

Drug self-administration studies have recently employed progressive ratio (PR) schedules to examine psychostimulant and opiate reinforcement. This review addresses the technical, statistical, and theoretical issues related to the use of the PR schedule in self-administration studies in rats. Session parameters adopted for use in our laboratory and the considerations relevant to them are described. The strengths and weaknesses of the PR schedule are also discussed.

Addiction is a chronic relapsing disorder characterized by the loss of control over drug intake, high motivation to obtain the drug, and a persistent craving for the drug. Accumulating evidence implicates cellular and molecular alterations within cortico-basal ganglia-thalamic circuitry in the development and persistence of this disease. The striatum is a heterogeneous structure that sits at the interface of this circuit, receiving input from a variety of brain regions (e.g., prefrontal cortex, ventral tegmental area) to guide behavioral output, including motor planning, decision-making, motivation and reward. However, the vast interconnectivity of this circuit has made it difficult to isolate how individual projections and cellular subtypes within this circuit modulate each of the facets of addiction. Here, we review the use of new technologies, including optogenetics and DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), in unraveling the role of the striatum in addiction. In particular, we focus on the role of striatal cell populations (i.e., direct and indirect pathway medium spiny neurons) and striatal dopaminergic and glutamatergic afferents in addiction-related plasticity and behaviors.