Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors.

BACKGROUND: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.

Age-dependent effects of environmental enrichment on spatial memory and neurochemistry.

Although aging and environmental stimulation are well-known to affect cognitive abilities, the question of whether aging effects can be distinguished in already-mature adult rats has not been fully addressed. In the present study, therefore, young and mature adult rats were housed in either enriched or standard conditions (EE or SC) for three months. Open-field (OFT) and radial-maze (RM) behavior, and ex-vivo contents of GABA and glutamate in hippocampus, and of dopamine and DOPAC in ventral striatum (VS) were analyzed and compared between the four groups. In OFT, young rats were more active than mature adults irrespective of the housing condition. Surprisingly, in the RM test, mature adults outperformed young counterparts except for the young-enriched rats, which showed a progressive improvement in RM performance. At the neurochemical level, young EE rats showed higher hippocampal glutamate and GABA concentrations, and DA turnover in VS, which correlated with RM performance. Altogether, the behavioral and cognitive strategies underlying habituation learning and spatial memory seem to be qualitatively different between the two ages analyzed. These results challenge the assumption that mature adult animals are always worse in learning and memory tasks. However, young rats benefited more from the social and physical stimulation provided by the enrichment than mature adult counterparts. The latter effect was evident not just on behavior, but also on brain neurochemistry.

Insula to ventral striatal projections mediate compulsive eating produced by intermittent access to palatable food.

Compulsive eating characterizes many binge-related eating disorders, yet its neurobiological basis is poorly understood. The insular cortex subserves visceral-emotional functions, including taste processing, and is implicated in drug craving and relapse. Here, via optoinhibition, we implicate projections from the anterior insular cortex to the nucleus accumbens as modulating highly compulsive-like food self-administration behaviors that result from intermittent access to a palatable, high-sucrose diet. We identified compulsive-like eating behavior in female rats through progressive ratio schedule self-administration and punishment-resistant responding, food reward tolerance and escalation of intake through 24-h energy intake and fixed-ratio operant self-administration sessions, and withdrawal-like irritability through the bottle brush test. We also identified an endocrine profile of heightened GLP-1 and PP but lower ghrelin that differentiated rats with the most compulsive-like eating behavior. Measures of compulsive eating severity also directly correlated to leptin, body weight and adiposity. Collectively, this novel model of compulsive-like eating symptoms demonstrates adaptations in insula-ventral striatal circuitry and metabolic regulatory hormones that warrant further study.