Clinical perception and management of Parkinson's disease during the COVID-19 pandemic: A Canadian experience.

BACKGROUND: The COVID-19 pandemic has necessitated the social isolation of the population and the rapid implementation of remote care for patients with neurodegenerative diseases. The objective of this study was to explore the perceived impact of confinement in patients with Parkinson's disease and document the effects of gender and living environment. METHODS: We recruited two cohorts from the Canadian provinces of Québec and Alberta, which differed in the dynamics of COVID-19 spreading at the time of the study, and administered a questionnaire on the perceived effects of confinement on daily living and disease management. RESULTS: The data reveals that approximately half of the patients experienced a change in one or more clinical symptoms, with differences observed between gender (e.g. day-to-day changes in slowness in men, aggravated headaches in women) and geographic location (e.g. increased depression in Alberta but reduced sleep quality in Québec). Furthermore, participants identifying as women or living in Alberta implemented more frequently home or online exercise. Lastly, high levels of satisfaction with phone or video consultations did not translate into a sustained interest to pursue this mode of healthcare. CONCLUSIONS: This study suggests that COVID-19-related confinement affected Parkinson's disease manifestation and management. Patients also reported varying levels of interest to continue remote care. A number of differences reported in our study were seemingly related to gender and living environment.

Dopamine in the oval bed nucleus of the stria terminalis contributes to compulsive responding for sucrose in rats.

Binge eating disorder (BED) is characterized by periods of excessive food intake combined with subjective feelings of loss of control. We examined whether sucrose bingeing itself leads to uncontrolled or compulsive responding and whether this effect is magnified following a period of abstinence. We then assessed dopamine (DA) modulation of inhibitory synaptic transmission in the oval bed nucleus of the stria terminalis (ovBNST) as a neural correlate of compulsive responding and whether this behavioral effect could be disrupted by DA blockade in the ovBNST. Over 28 days, male Long-Evans rats (n = 8-16 per group) had access to 10% sucrose and food (12 or 24 h), 0.1% saccharin and food (12 h), or food alone (12 h). Compulsive responding was assessed following 1 or 28 days of sucrose abstinence using a conditioned suppression paradigm. Only rats given 12 h access to sucrose developed binge-like intake, manifested as copious intake within the first hour; compulsive responding was significantly elevated in this group following 28 days of abstinence. In parallel, the effect of DA on ovBNST inhibitory transmission switched from a reduction to a potentiation; the effect, although observable after 1 day, was more pronounced and sustained following 28 days of abstinence. Intra-ovBNST infusions of a DA D1 receptor antagonist (0.8 µg/µl SCH-23390) reversed the blockade of conditioned suppression, thereby confirming the causal relationship between ovBNST DA modulation of γ-aminobutyric acid transmission and alterations in conditioned suppression following binge-like intake of sucrose.

A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats.

Chronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.

GluN2B-containing NMDA receptors blockade rescues bidirectional synaptic plasticity in the bed nucleus of the stria terminalis of cocaine self-administering rats.

Drugs of abuse have detrimental effects on homeostatic synaptic plasticity in the motivational brain network. Bidirectional plasticity at excitatory synapses helps keep neural circuits within a functional range to allow for behavioral flexibility. Therefore, impaired bidirectional plasticity of excitatory synapses may contribute to the behavioral hallmarks of addiction, yet this relationship remains unclear. Here we tracked excitatory synaptic strength in the oval bed nucleus of the stria terminalis (ovBNST) using whole-cell voltage-clamp recordings in brain slices from rats self-administering sucrose or cocaine. In the cocaine group, we measured both a persistent increase in AMPA to NMDA ratio (A:N) and slow decay time of NMDA currents throughout the self-administration period and after withdrawal from cocaine. In contrast, the sucrose group exhibited an early increase in A:N ratios (acquisition) that returned toward baseline values with continued self-administration (maintenance) and after withdrawal. The sucrose rats also displayed a decrease in NMDA current decay time with continued self-administration (maintenance), which normalized after withdrawal. Cocaine self-administering rats exhibited impairment in NMDA-dependent long-term depression (LTD) that could be rescued by GluN2B-containing NMDA receptor blockade. Sucrose self-administering rats demonstrated no impairment in NMDA-dependent LTD. During the maintenance period of self-administration, in vivo (daily intraperitoneally for 5 days) pharmacologic blockade of GluN2B-containing NMDA receptors did not reduce lever pressing for cocaine. However, in vivo GluN2B blockade did normalize A:N ratios in cocaine self-administrating rats, and dissociated the magnitude of ovBNST A:N ratios from drug-seeking behavior after protracted withdrawal. Altogether, our data demonstrate when and how bidirectional plasticity at ovBNST excitatory synapses becomes dysfunctional with cocaine self-administration and that NMDA-mediated potentiation of AMPA receptors in this region may be part of the neural circuits of drug relapse.

D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.

Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction.