MPEP, a selective metabotropic glutamate receptor 5 antagonist, attenuates conditioned taste aversion in rats

Schachtman, Todd R.; Bills, Carla; Ghinescu, Rodica; Murch, Kevin; Serfózó, Péter; Simonyi, Ágnes

doi:10.1016/s0166-4328(02)00378-9

Cited by 30 publications

(18 citation statements)

References 35 publications

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“…The involvement of glutamate in this process is supported by evidence linking glutamatergic activity to other forms of associative learning. For example, blockade of metabotropic glutamate receptor 5 (mGluR5) attenuates conditioned taste aversion (CTA, i.e., suppression of a palatable cue when paired with an aversive unconditioned stimulus such as LiCl) in rats (Schachtman et al , 2003, Simonyi et al , 2009) and increased phosphorylated NMDA subunit NR1 (p-NR1) expression in the prefrontal cortex has been observed during the acquisition, but not expression, of CTA (Marotta et al , 2014). Similarly, inhibition of the vesicular glutamate transporter (VGLUT) with intracerebroventricular Chicago sky blue 6B (CSB6B) attenuates conditioned place preference (CPP) for methamphetamine (He et al , 2014) and a similar disruption in morphine, methamphetamine, and cocaine CPP learning has been observed with activation of GLT-1 using gene transfer (Fujio et al , 2005) or MS-153 administration (Nakagawa et al , 2005).…”

Section: Discussionmentioning

confidence: 99%

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

Freet

Lawrence

2015

Physiology & Behavior

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Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200 mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1 hour and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24 hours for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice.

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Section: Discussionmentioning

confidence: 99%

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

Freet

Lawrence

2015

Physiology & Behavior

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“…As the priming dose of ethanol was very small (on average 0.04 g/ kg), it is likely that MPEP reduced the ability of the stimulus complex associated with ethanol (ie the environmental cues and orosensory properties of ethanol) to reinstate lever pressing rather than counteracted the central pharmacological effects of ethanol. Similarly, MPEP has been shown to attenuate the expression of other conditioned behaviors, including conditioned fear, morphine-and cocaine-induced place preference, and taste aversion (Schulz et al, 2001;Popik and Wrobel, 2002;McGeehan and Olive, 2003;Schachtman et al, 2003). Effect of MPEP on alcohol relapse P Bäckström et al…”

Section: Discussionmentioning

confidence: 99%

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Bäckström

Bachteler

Koch

et al. 2003

Neuropsychopharmacol

235

178

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The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.

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“…administration of the mGluR1 antagonist (S)-(+)-alpha-amino-4carboxy-2-methylbenzene-acetic acid (LY-367385) impaired LTP and spatial reference, but not working memory in rats in a radial maze task, while locomotor activity was not affected by this treatment [14]. In contrast, conditioned taste aversion was not impaired by systemic administration of AIDA [15], suggesting that not all forms of learning and memory are mediated by mGluR1.…”

Section: Role Of Mglur In Learning and Memory Processes And Potentialmentioning

confidence: 99%

“…administration of MPEP resulted in LTP impairment in the dentate gyrus of the hippocampus and impaired spatial working memory tested in the Y-maze [4]. Moreover, mGluR5 also seem to play a role in the formation of taste memories, since systemic administration of MPEP attenuated conditioned taste aversion (CTA) in rats [15]. A more recent study evaluated the effects of MTEP on CTA after local injections into the insular cortex and the basolateral nucleaus of the amygdala (BLA).…”

Section: Role Of Mglur In Learning and Memory Processes And Potentialmentioning

confidence: 99%

Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders

Gravius¹,

Pietraszek²,

Dekundy³

et al. 2010

CTMC

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Since more than one decade, metabotropic glutamate receptors have been under investigation as targets for various CNS disorders such as anxiety, pain, depression, schizpohrenia, Alzheimer's disease and Parkinson's disease. It has been shown that some mGluRs play a crucial role in cognitive processes such as learning and memory, which was initially, demonstrated using knockout mice for each receptor subtype. Later, selective pharmacological tools were developed allowing more specific examinations of the involvement of mGluR1-8 in various forms of learning and memory. Ligands for group I and II mGluRs have been proposed as promising candidates for the treatment of cognitive disorders such as schizophrenia, Fragile X syndrome, Alzheimer's and Parkinson's disease and post traumatic stress disorder, of which some have made it to clinical testing. The present paper reviews relevant data on the role of mGluRs in learning and cognition processes focusing on their utility as targets for cognition enhancement in several CNS diseases.

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MPEP, a selective metabotropic glutamate receptor 5 antagonist, attenuates conditioned taste aversion in rats

Cited by 30 publications

References 35 publications

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders

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