Depletion of the glycine alpha 2 receptor promotes reward-related behaviors
The striatum integrates cortical sensory information with motivational inputs originating in the ventral tegmental area. This integration allows for adequate goal-directed behavior, and impaired neurotransmission can induce reward-related psychopathologies such as drug abuse and psychosis. Here, we investigated the role of the glycine alpha 2 receptor (GlyRa2) in reward-related behaviors. Glycine receptors are pentameric ionotropic receptors that are composed of alpha (a1-a4) and/or beta subunits that form an ionic pore permeable to chloride. During development, most GlyRs are homomeric, composed of alpha 2 subunits. Expression of alpha 2 rapidly declines postnatally, suggesting its importance during early development. Indeed, we have shown proliferation and migration defects in layer V of the cortex, an area that provides input to the striatum. Interestingly, and in contrast to the idea of a restricted role in development, we have recently identified GlyRa2 as the only functional glycine receptor in adult striatum. We therefore investigated striatum-mediated behavior in GlyRa2 KO mice. We show a sensitized response to amphetamine (5mg/kg, i.p.) in GlyRa2 KO mice in a horizontal locomotor task, yet no changes in baseline locomotor activity. Accordingly, we exhibit increased nose poke behavior in an appetitive conditioning task that is only apparent at higher order reward schedules, which indicates altered motivation. Yet, GlyRa2 KO animals reveal greater extinction on the first extinction trial. In order to elucidate whether enhanced nose poking indeed reflected enhanced motivation, we performed a T-maze task. We found increased motivation, enhanced associative learning, but no changes in the hedonic response. We conclude that GlyRa2 plays a major role in striatal reward-related behavior. These processes are implicated in major psychopathologies, including schizophrenia and drug abuse, and modulation thereof can prove to be highly beneficial towards the development of targeted treatment.
The present research demonstrates a crucial role for the glycine alpha 2 receptor in processes that are disrupted in severe pathologies such as schizophrenia and drug abuse. While it was long thought that this receptor was transiently expressed during development, we now know that it is the only functional glycine receptor in brain areas that are key to the development of these pathologies. We thus reveal the glycine alpha 2 receptor as a novel, promising target in striatum-dependent pathologies.
Résumé en Français:
Le système de récompense passe par un réseau de neurones du striatum, région du cerveau impliquée dans le circuit de la récompense. Cette communication passe par un réseau de contacts (synapses) entre neurones qui utilisent des récepteurs pour cette transmission. Dans ce travail, en utilisant des tests comportementaux, nous montrons qu’un des récepteurs, appelé « Récepteur a2 à la Glycine» joue un rôle important dans le comportement lié à la récompense. Sachant que des altérations de cette transmission sont à la base de pathologies comme l’addiction et les psychoses, on peut estimer que la découverte de nouvelles drogues ciblant ce récepteur constitue une nouvelle approche thérapeutique.
Samenvatting in het Nederlands:
Het striatum is een structuur in de hersenen die een cruciale rol speelt in beloningsleren, en verstoorde informatieoverdracht hier kan leiden tot drugverslaving en psychose. Belangrijke modulatoren van de informatieoverdracht zijn neurotransmitter receptoren. Wij hebben de rol onderzocht van een dergelijke receptor, GlyRa2. Lang werd gedacht dat deze receptor enkel voorkwam tijdens de ontwikkeling. Nu weten we echter dat in het striatum, GlyRa2 ook op volwassen leeftijd een belangrijke rol speelt. In ons onderzoek tonen we dat beloningsleren inderdaad is aangetast in muizen waarin deze receptor ontbreekt. GlyRa2 belooft dus een interessante therapeutische target te zijn voor striatum-afhankelijke psychopathologie.
Keywords:
Striatum,
Reward,
glycine receptor,
Schizophrenia,
Behavior, Animal
Conference:
6th Belgian Brain Congress, MONS, Belgium, 8 Oct - 8 Oct, 2016.
Presentation Type:
Poster Presentation
Topic:
Brain and brain diseases: between heredity and environment
Citation:
Piccart
E
(2016). Depletion of the glycine alpha 2 receptor promotes reward-related behaviors.
Conference Abstract:
6th Belgian Brain Congress.
doi: 10.3389/conf.fnagi.2016.03.00085
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Received:
17 Jul 2016;
Published Online:
17 Jul 2016.
*
Correspondence:
Dr. Elisabeth Piccart, UHasselt, Hasselt, Belgium, elisabeth.piccart@uhasselt.be