Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats

Sukhotina, I. A.; Dravolina, Olga A.; Novitskaya, Yulia; Zvartau, Edwin; Danysz, Wojciech; Bespalov, Anton

doi:10.1007/s00213-007-0953-2

Cited by 43 publications

(44 citation statements)

References 41 publications

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“…Similarly, negative mGluR5 allosteric modulation by RO4917523 and MTEP had no effect on this dissociable aspect of 'waiting' impulsivity. A recent study provides additional evidence for this distinction; a selective mGluR1 antagonist, EMQMCM, reportedly enhanced motor impulsivity in the differential reinforcement of low rates (DRL) task but attenuated choice impulsivity by increasing tolerance of delayed rewards (Sukhotina et al 2008). Furthermore, MK801 reportedly improved choice impulsivity by appearing to decrease sensitivity to delayed reinforcement (Yates et al 2014).…”

Section: Discussionmentioning

confidence: 96%

Dissociable effects of mGluR5 allosteric modulation on distinct forms of impulsivity in rats: interaction with NMDA receptor antagonism

et al. 2015

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Section: Discussionmentioning

confidence: 96%

Dissociable effects of mGluR5 allosteric modulation on distinct forms of impulsivity in rats: interaction with NMDA receptor antagonism

et al. 2015

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“…First, rats (n=12 for experiments with memantine and n=9 in studies on A-705253) were shaped to lever press for food pellet delivery and then were taken through several consecutive training stages as described earlier (Sukhotina et al, 2008). All animals were trained in parallel and needed about 50 sessions to achieve the final stage of the training.…”

Section: Delayed Non-matching To Position (Dnmtp) Testmentioning

confidence: 99%

The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile

Vengeliene

Moeller

Meinhardt

et al. 2015

Neuropsychopharmacol

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Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side effects. One of the key intracellular events resulting from stimulation of NMDAR is activation of calpains-calcium-dependent cysteine proteases. Here we studied whether inhibition of calpains would produce therapeutic-like effects of NMDAR antagonists but without their NMDAR-mediated side-effect profile. The calpain inhibitor A-705253 (3-10 mg/kg) was tested in a model of cue-induced reinstatement of alcohol-seeking behavior in post-dependent Wistar rats and in an alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats, two behavioral models for alcohol-seeking and relapse, respectively. We also tested the effect of A-705253 on the saccharine deprivation effect (SDE) as a selectivity measure. Acute treatment with A-705253 dose-dependently reduced cue-induced reinstatement of alcohol-seeking behavior. Repeated administration of A-705253 caused significant reductions of relapse-like excessive alcohol intake during the post-abstinence drinking days, an effect that persisted during two more successive drug-free drinking weeks, which was selective for the ADE as the SDE was unaffected. However, A-705253 did not produce psychostimulant, cognition impairing (delayed-matching-to-position), or psychotomimetic effects (specifically, phencyclidine discriminative stimulus effects). Taken together, these results demonstrate the involvement of calpains in alcohol-seeking and relapse and present a rationale for a novel pharmacological intervention that may reduce craving and relapse with minimal side effects in alcohol-dependent patients.

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“…Experiments were conducted in operant chambers (MED Associates, East Fairfield, U.S.A.) (Sukhotina et al, 2008). Rats were trained to lever-press for food and to learn the DNMTP rule.…”

Section: Delayed Non-matching To Position (Dnmtp) Taskmentioning

confidence: 99%

Impaired Cognition after Stimulation of P2Y1 Receptors in the Rat Medial Prefrontal Cortex

Koch

Bespalov

Drescher

et al. 2014

Neuropsychopharmacol

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We hypothesize that cortical ATP and ADP accumulating in the extracellular space, eg during prolonged network activity, contribute to a decline in cognitive performance in particular via stimulation of the G protein-coupled P2Y 1 receptor (P2Y 1 R) subtype. Here, we report first evidence on P2Y 1 R-mediated control of cognitive functioning in rats using bilateral microinfusions of the selective agonist MRS2365 into medial prefrontal cortex (mPFC). MRS2365 attenuated prepulse inhibition of the acoustic startle reflex while having no impact on startle amplitude. Stimulation of P2Y 1 Rs deteriorated performance accuracy in the delayed non-matching to position task in a delay dependent manner and increased the rate of magazine entries consistent with both working memory disturbances and impaired impulse control. Further, MRS2365 significantly impaired performance in the reversal learning task. These effects might be related to MRS2365-evoked increase of dopamine observed by microdialysis to be short-lasting in mPFC and long-lasting in the nucleus accumbens. P2Y 1 Rs were identified on pyramidal cells and parvalbumin-positive interneurons, but not on tyrosine hydroxylase-positive fibers, which argues for an indirect activation of dopaminergic afferents in the cortex by MRS2365. Collectively, these results suggest that activation of P2Y 1 Rs in the mPFC impairs inhibitory control and behavioral flexibility mediated by increased mesocorticolimbic activity and local disinhibition.

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Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats

Abstract: Blockade of mGlu1 receptors improves working memory and reduces impulsive choice at the doses that have no effects on time perception but appear to facilitate impulsive action.

Cited by 43 publications

References 41 publications

Dissociable effects of mGluR5 allosteric modulation on distinct forms of impulsivity in rats: interaction with NMDA receptor antagonism

Dissociable effects of mGluR5 allosteric modulation on distinct forms of impulsivity in rats: interaction with NMDA receptor antagonism

The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile

Impaired Cognition after Stimulation of P2Y1 Receptors in the Rat Medial Prefrontal Cortex

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