Natural Reward Experience Alters AMPA and NMDA Receptor Distribution and Function in the Nucleus Accumbens

Natural reward and drugs of abuse converge upon the mesolimbic system which mediates motivation and reward behaviors. Drugs induce neural adaptations in this system, including transcriptional, morphological, and synaptic changes, which contribute to the development and expression of drug-related memories and addiction. Previously, it has been reported that sexual experience in male rats, a natural reward behavior, induces similar neuroplasticity in the mesolimbic system and affects natural reward and drug-related behavior. The current study determined whether sexual experience causes long-lasting changes in mating, or ionotropic glutamate receptor trafficking or function in the nucleus accumbens (NAc), following 3 different reward abstinence periods: 1 day, 1 week, or 1 month after final mating session. Male Sprague Dawley rats mated during 5 consecutive days (sexual experience) or remained sexually naïve to serve as controls. Sexually experienced males displayed facilitation of initiation and performance of mating at each time point. Next, intracellular and membrane surface expression of N-methyl-D-aspartate (NMDA: NR1 subunit) and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA: GluA1, GluA2 subunits) receptors in the NAc was determined using a bis(sulfosuccinimidyl)suberate (BS3) protein cross-linking assay followed by Western Blot analysis. NR1 expression was increased at 1 day abstinence both at surface and intracellular, but decreased at surface at 1 week of abstinence. GluA2 was increased intracellularly at 1 week and increased at the surface after 1 month of abstinence. Finally, whole-cell patch clamp electrophysiological recordings determined reduced AMPA/NMDA ratio of synaptic currents in NAc shell neurons following stimulation of cortical afferents in sexually experienced males after all reward abstinence periods. Together, these data show that sexual experience causes long-term alterations in glutamate receptor expression and function in the NAc. Although not identical, this sex experience-induced neuroplasticity has similarities to that caused by psychostimulants, suggesting common mechanisms for reinforcement of natural and drug reward

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Increased drinking after intra-striatal injection of the dopamine D2/D3 receptor agonist quinpirole in the rat

RATIONALE Dopamine D2 receptor hyperactivity has been implicated in the development of psychogenic polydipsia in schizophrenic patients. Repeated treatment with dopamine agonists, including the D2/D3 agonist quinpirole, has been shown to induce hyperdipsia in a number of animal models. Despite these observations, obtained with systemic administrations, little attempt has been made to investigate where in the brain dopamine agonists act to induce hyperdipsia. OBJECTIVE The present study investigates the effects of repeated intra-caudate infusions of quinpirole on the intake of water by rats tested under free-drinking conditions. MATERIALS AND METHODS Rats with bilateral cannulae placed into the anterior, central or posterior caudate received quinpirole microinfusions (1 μg/side) for five consecutive days in their home cage. Water intake was measured 15 and 60 min after the treatment. RESULTS When injected in the central caudate, quinpirole increased water intake, and this effect progressively increased over sessions, indicating the development of sensitization. When injected in the posterior caudate, the dipsogenic effect of quinpirole was less intense and did not undergo sensitization. The infusion of quinpirole in the anterior caudate did not affect drinking. CONCLUSION The present study shows that caudate D2/3 receptors play an important role in the development of quinpirole-induced hyperdipsia, an animal model of psychotic polydipsia