Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

Abstract

Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D 2 receptors in cocaine addiction. For example, an inverse relationship between D 2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensitivity to the abuse-related effects of cocaine. Similarly, both D 2 receptor availability and cocaine selfadministration can be altered by chronic drug administration and fluctuations in hormone levels. In addition, cocaine self-administration can be altered in an orderly fashion by presentation of an acute stressor, such as acting as an intruder into an unfamiliar social group, which can shift the cocaine dose-response curve to the left in subordinate monkeys and to the right in dominant animals, suggesting an interaction between social variables and acute stressors. Conversely, irrespective of social rank, acute environmental enrichment, such as increasing the size of the living space, shifts the cocaine dose-response curve to the right. These findings highlight a pervasive influence of the environment in modifying the reinforcing effects of cocaine and strongly implicate brain D 2 receptors.

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…In humans, prosocial behaviors such as physical activity and engaging in high sensation experiences may be effective in reducing drug use. These findings parallel those observed in rats (Klebaur et al, 2001b;Smith and Pitts, 2011), and results from monkeys suggest that enriching stimuli may decrease drug reinforcement (Nader et al, 2008). Not only do alternative appetitive stimuli reduce drug self-administration generally, the effectiveness of alternative stimuli may be greatest among individuals prone to addiction.…”

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…27 Thus, in NAcc and striatum, the reinforcing effect of nicotine and other psychostimulants is characterized by increasing DA transmission that binds to the DA Rs, which can further induce DA R downregulation. 6,7,30,31 James et al 23 proved the existence of direct brain-testis pathway that controls testicular function using retrograde viral tracing from the testicular TH expressing nerve fibers to the midbrain DAergic area. The presence of DA and DAergic marker, TH, in different testicular tissues further establish the paracrine action of DA in spermatogenesis.…”

“…27 DA transporter blockade by psychostimulants also cause elevation of extracellular DA and DA R downregulation, resulting in addictive behavior. 30,31 Interestingly, local effect of BDNF, like DA, is observed in several peripheral organs like testis, thyroid, and adrenal upon drug abuse, 32,33 and activation of Trkβ R releases intracellular calcium through phospholypase C, which subsequently potentiates BDNF release, 34 but the interaction between testicular toxicity and local NT system, ie, DA and BDNF is yet to be understood.…”

Socioeconomic stress by dopamine receptor 2 gene interactions in the development of obesity

“…It is know that DRD2 receptors in the striatum play a key role in the development of addiction to natural rewards (Volkow, Wang, Fowler, & Telang, 2008). Low availability of D2 receptors predisposes to the development of compulsive behavior as well (Nader, Czoty, Gould, & Riddick, 2008;Volkow, et al, 2008). Compulsive behavior can also be linked with addictive behaviors such as in one study where the link between coping motives and chronic alcohol outcomes was moderated by the Taq1A allele (van der Zwaluw, Kuntsche, & Engels, 2011).…”