Individual differences and social influences on the neurobehavioral pharmacology of abused drugs

Abstract

The interaction of drugs with biologic targets is a critical area of research, particularly for the development of medications to treat substance use disorders. In addition to understanding these drug-target interactions, however, there is a need to understand more fully the psychosocial influences that moderate these interactions. The first section of this review introduces some examples from human behavioral pharmacology that illustrate the clinical importance of this research. The second section covers preclinical evidence to characterize some of the key individual differences that alter drug sensitivity and abuse vulnerability, related primarily to differences in response to novelty and impulsivity. Evidence is presented to indicate that critical neuropharmacological mechanisms associated with these individual differences involve integrated neurocircuits underlying stress, reward, and behavioral inhibitory processes. The third section covers social influences on drug abuse vulnerability, including effects experienced during infancy, adolescence, and young adulthood, such as maternal separation, housing conditions, and social interactions (defeat, play, and social rank). Some of the same neurocircuits involved in individual differences also are altered by social influences, although the precise neurochemical and cellular mechanisms involved remain to be elucidated fully. Finally, some speculation is offered about the implications of this research for the prevention and treatment of substance abuse.

Fig. 1.

Schematic of brain changes in HR rats compared with LR rats. Regions in blue represent primarily reward-relevant central structures, regions in green represent primarily stress-related central structures, and region in red is a peripheral stress-related gland. Brain regions: ACe, central nucleus of amygdala; Hippo, hippocampus; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; VTA, ventral tegmental area. Cellular changes: CORT, corticosterone; DA, dopamine; DAT, dopamine transporter; NARP, neuronal activity-regulated pentraxin; FGFR1, fibroblast growth factor receptor 1; TH, tyrosine hydroxylase.

Fig. 2.

Schematic of brain changes in isolate-housed rats compared with socially enriched rats. Regions in blue represent primarily reward-relevant central structures, regions in green represent primarily stress-related central structures, and the region in red is a peripheral stress-related gland. Note that the overlap in circuitry depicted previously in Fig. 1 suggests that HR rats (Fig. 1) and isolated rats (this figure) share similar neural mechanisms. Brain regions: ACe, central nucleus of amygdala; Hippo, hippocampus; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; VTA, ventral tegmental area. Cellular changes: CAT, choline acetyltransferase; CORT, corticosterone; CREB, cAMP response element binding; DA, dopamine; NE, norepinephrine; NGF, nerve growth factor.