Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Abstract

Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BP ND )) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n = 10) or one that received equal-time health education training (n = 9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [ 18 F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BP ND . At baseline, striatal D2/D3 BP ND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BP ND , whereas those in the education group did not. There were no changes in D2/D3 BP ND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

Reduced effects of age on dopamine D2 receptor levels in physically active adults

“…Although several studies have shown causal links for short-term activity interventions and DRD2 receptors in animals, humans with Parkinson’s Disease, and human methamphetamine users (Fisher et al, 2013; Robertson et al, 2016; Vuckovic et al, 2010), our data do not directly show that physical activity causally ameliorates DRD2 loss in normal aging. It may be that individuals with higher DRD2 in the ventral striatum, an area associated with reward functions, are more motivated to be physically active as they age.…”

“…Intriguingly, exercise training was observed to increase striatal DRD2 receptor availability in humans with Parkinson’s disease and methamphetamine users (Fisher et al, 2013; Robertson et al, 2016). However, although aging, Parkinson’s disease, methamphetamine use and MPTP neurotoxicity all impact dopamine functions, the specificity of their effects on the dopamine system differs significantly.…”

Cigarette Use and Striatal Dopamine D2/3 Receptors: Possible Role in the Link between Smoking and Nicotine Dependence

“…One approach to enhance striatal D2/3 BP nd is through exercise training, as has been suggested for patients with stimulant use disorder (Robertson et al, 2015). Exercise was proposed as a smoking-cessation aid long ago, and there are some reports of benefits from exercise in reducing tobacco consumption, albeit with limited evidence of long-term benefit (Ussher et al, 2014).…”

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

“…Future prospective studies may include collecting those measures as well as investigating exercise interventions to examine D 2/3 R transformations as BMI decreases. In fact, one study using [ 18 F]fallypride has recently demonstrated that exercise intervention for 8 weeks, compared with psychoeducation, normalized lower striatal D 2/3 Rs in humans with methamphetamine-use disorder (Robertson et al, 2015). Second, although research participants were gender-and age-matched in the primary between-group comparisons, the cohort for the secondary correlational analyses was heavily dominated by males (33 males vs 9 females); thus, further correlational analyses confirming our findings are warranted in a gender-balanced cohort.…”