Rationale In drug self-administration procedures, extended-access test sessions allow researchers to model maladaptive patterns of excessive and escalating drug intake that are characteristic of human substance-abusing populations. Objectives The purpose of the present study was to examine the ability of aerobic exercise to decrease excessive and escalating patterns of drug intake in male and female rats responding under extended-access conditions. Methods Male and female Long-Evans rats were obtained at weaning and divided into sedentary (no running wheel) and exercising (running wheel) groups immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and allowed to self-administer cocaine under positive reinforcement contingencies. In Experiment 1, cocaine self-administration was examined during 23-hour test sessions that occurred every four days. In Experiment 2, the escalation of cocaine intake was examined during daily 6-hour test sessions over 14 consecutive days. Results In Experiment 1, sedentary rats self-administered significantly more cocaine than exercising rats during uninterrupted 23-hour test sessions, and this effect was apparent in both males and females. In Experiment 2, sedentary rats escalated their cocaine intake to a significantly greater degree than exercising rats over the 14 days of testing. Although females escalated their cocaine intake to a greater extent than males, exercise effectively attenuated the escalation of cocaine intake in both sexes. Conclusions These data indicate that aerobic exercise decreases maladaptive patterns of excessive and escalating cocaine intake under extended-access conditions.

Background Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats. Methods Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) and exercising (access to wheel) groups for the duration of the study. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine for 14 days. After training, saline was substituted for cocaine and responding was allowed to extinguish, after which cocaine-primed reinstatement was examined in both groups. Following this test, cocaine self-administration was re-established in both groups for a 5-day period. Next, a second period of abstinence occurred in which both cocaine and the cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced reinstatement was examined in both groups. Results Sedentary and exercising rats exhibited similar levels of cocaine self-administration, but exercising rats responded less than sedentary rats during extinction. In tests of cocaine-primed and cue-induced reinstatement, exercising rats responded less than sedentary rats, and this effect was apparent in both males and females. Conclusions These data indicate that long-term access to a running wheel decreases drug-primed and cue-induced reinstatement, and that physical activity may be effective at preventing relapse in substance-abusing populations.

BackgroundAbnormal antagonist leg muscle activity could indicate increased muscle co-contraction and clarify mechanisms of balance impairments in Parkinson’s disease (PD). Prior studies in carefully selected patients showed PD patients demonstrate earlier, longer, and larger antagonist muscle activation during reactive balance responses to perturbations.Research questionHere, we tested whether antagonist leg muscle activity was abnormal in a group of PD patients who were not selected for phenotype and most of whom had volunteered for exercise-based rehabilitation.MethodsWe compared antagonist activation during reactive balance responses to multidirectional support-surface translation perturbations in 31 patients with mild-moderate PD (age 68±9; H&Y 1–3; UPDRS-III 32±10) and 13 matched individuals (age 65±9). We quantified modulation of muscle activity (i.e., the ability to activate and inhibit muscles appropriately according to the perturbation direction) using modulation indices (MI) derived from minimum and maximum EMG activation levels observed across perturbation directions.ResultsAntagonist leg muscle activity was abnormal in unselected PD patients compared to controls. Linear mixed models identified significant associations between impaired modulation and PD (P<0.05) and PD severity (P<0.01); models assessing the entire sample without referencing PD status identified associations with balance ability (P<0.05), but not age (P = 0.10).SignificanceAntagonist activity is increased during reactive balance responses in PD patients who are not selected on phenotype and are candidates for exercise-based rehabilitation. This activity may be a mechanism of balance impairment in PD and a potential rehabilitation target or outcome measure.

Impaired set shifting is associated with previous falls in older adults with and without PD. Set shifting may be useful to include in fall risk assessments, particularly when global cognitive measures are within reference limits.

Although Parkinson disease (PD) causes profound balance impairments, we know very little about how PD impacts the sensorimotor networks we rely on for automatically maintaining balance control. In young healthy people and animals, muscles are activated in a precise temporal and spatial organization when the center of body mass (CoM) is unexpectedly moved that is largely automatic and determined by feedback of CoM motion. Here, we show that PD alters the sensitivity of the sensorimotor feedback transformation. Importantly, sensorimotor feedback transformations for balance in PD remain temporally precise, but become spatially diffuse by recruiting additional muscle activity in antagonist muscles during balance responses. The abnormal antagonist muscle activity remains precisely time-locked to sensorimotor feedback signals encoding undesirable motion of the body in space. Further, among people with PD, the sensitivity of abnormal antagonist muscle activity to CoM motion varies directly with the number of recent falls. Our work shows that in people with PD, sensorimotor feedback transformations for balance are intact but disinhibited in antagonist muscles, likely contributing to balance deficits and falls.