Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice

Escher, Tobie; Call, Stanford B.; Blaha, Charles D.; Mittleman, Guy

doi:10.1007/s00213-006-0465-5

Cited by 25 publications

(19 citation statements)

References 74 publications

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“…SIP is consistently reduced by acute treatments with dopamine (DA) receptor agonists or antagonists [38], [39], [40], [41]. Furthermore, D2-like receptor binding was increased in the nucleus accumbens (NAc), medial prefrontal cortex, amygdala and ventral tegmental areas in animals that were high drinkers in the SIP paradigm and D1-like receptors were decreased in the same areas [42].…”

Section: Discussionmentioning

confidence: 99%

Increased Drinking following Social Isolation Rearing: Implications for Polydipsia Associated with Schizophrenia

2013

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Primary polydipsia, excessive drinking without known medical cause, is especially associated with a diagnosis of schizophrenia. We used animal models of schizophrenia-like symptoms to examine the effects on schedule-induced polydipsia: post-weaning social isolation rearing, subchronic MK-801 treatment (an NMDA-receptor antagonist) or the two combined. Male, Sprague-Dawley rats reared in groups or in isolation beginning at postnatal day 21 were further divided to receive subchronic MK-801 (0.5 mg/kg twice daily) or saline for 7 days beginning on postnatal day 62. Following a 4-day withdrawal period, all groups were trained on a schedule-induced polydipsia paradigm. Under food-restriction, animals reared in isolation and receiving food pellets at 1-min intervals developed significantly more drinking behavior than those reared with others. The addition of subchronic MK-801 treatment did not significantly augment the amount of water consumed. These findings suggest a predisposition to polydipsia is a schizophrenia-like behavioral effect of post-weaning social isolation.

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Section: Discussionmentioning

confidence: 99%

Increased Drinking following Social Isolation Rearing: Implications for Polydipsia Associated with Schizophrenia

2013

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“…The enhanced ethanol preference of Avpr1a KO mice was dramatically and reversibly attenuated by treatment with NMDA antagonists, such as MK801 and ifenprodil, whereas no significant difference was seen after treatment with naltrexone, a nonselective opioid receptor antagonist. The NMDA receptor is thought to be a target of drug therapy for alcoholics (17). Activation of the NMDA receptor by increased glutamate release and a decrease in glutamate reuptake, as well as increased NMDA receptor density, can lead to activation of Ca 2ϩ influx into the neurons and dynamic modulation of the actin cytoskeleton (25,33,38,40,55).…”

Section: Regulation Of Alcohol Preference By Avpmentioning

confidence: 99%

Alcohol preference in mice lacking the Avpr1a vasopressin receptor

Sanbe¹,

Takagi²,

Fujiwara³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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[Arg(8)]-vasopressin (Avp), a nonapeptide hormone, is known to regulate blood pressure, water balance, and a variety of behaviors such as anxiety, aggression, and bonding. Although some evidence that Avp modifies ethanol consumption and some of the effects of ethanol on behavior have been reported, the role of Avp in alcohol consumption and preference is poorly understood. The Avp1a receptor (Avpr1a) is ubiquitously expressed in the central nervous system. To determine the role of Avp signaling on the behavioral effects of alcohol, we examined voluntary ethanol consumption in mice with targeted disruptions of the Avpr1a knockout (Avpr1a KO) gene. Avpr1a KO mice displayed both increased ethanol consumption and preference compared with wild-type (WT) mice. Enhanced ethanol consumption was dramatically and reversibly reduced by treatment with N-methyl-D-aspartic acid antagonists. Basal glutamate release was elevated around the striatum in Avpr1a KO mice. Elevation of extracellular glutamate was also produced in WT mice by local application of an Avpr1a antagonist though a dialysis probe, and this elevation was quickly reversed by stopping the perfusion. These results suggest that Avp can inhibit the release of glutamate from the presynaptic terminal via the Avp1a receptor and that elevation of glutamate levels owing to loss of the inhibitory effect via Avp-Avpr1a signaling may play an important role in the preference for ethanol.

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“…[149] Memantine has been shown to reduce alcohol cravings in pre-clinical studies, [150–153] and alcohol dependence is known to be co-morbid with MDD. [154,155] In the Finnish study, abstinence was not required and both treatments significantly reduced depression and anxiety (primary outcome measures) without significant differences in treatment groups or in cognitive functioning scores.…”

Section: Therapeuticsmentioning

confidence: 99%

Targeting the Glutamatergic System to Treat Major Depressive Disorder

Mathews

Henter

Zarate

2012

Drugs

202

141

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Major depressive disorder (MDD) is a severe, debilitating medical illness that affects millions of individuals worldwide. The young age of onset and chronicity of the disorder has a significant impact on the long-term disability that affected individuals face. Most existing treatments have focused on the ‘monoamine hypothesis’ for rational design of compounds. However, patients continue to experience low remission rates, residual subsyndromal symptoms, relapses and overall functional impairment. In this context, growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of MDD, and discuss the efficacy of glutamatergic agents as novel therapeutics. Preliminary clinical evidence has been promising, particularly with regard to the N-methyl-D-aspartate (NMDA) antagonist ketamine as a ‘proof-of-concept’ agent. The review also highlights potential molecular and inflammatory mechanisms that may contribute to the rapid antidepressant response seen with ketamine. Because existing pharmacological treatments for MDD are often insufficient for many patients, the next generation of treatments needs to be more effective, rapid acting and better tolerated than currently available medications. There is extant evidence that the glutamatergic system holds considerable promise for developing the next generation of novel and mechanistically distinct agents for the treatment of MDD.

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Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice

Abstract: In addition to reducing alcohol drinking, both drugs had other behavioral effects that included reductions in regulatory drinking. These results suggest that the therapeutic utility of these drugs for ameliorating human alcohol addiction remains questionable.

Cited by 25 publications

References 74 publications

Increased Drinking following Social Isolation Rearing: Implications for Polydipsia Associated with Schizophrenia

Increased Drinking following Social Isolation Rearing: Implications for Polydipsia Associated with Schizophrenia

Alcohol preference in mice lacking the Avpr1a vasopressin receptor

Targeting the Glutamatergic System to Treat Major Depressive Disorder

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