Dataset Information

Selective and interactive effects of D₂ receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

ABSTRACT:

Background

Metabotropic glutamate receptor 4 (mGluR4) and dopamine D₂ receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D₂ receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D₂ receptor antagonist eticlopride, on two distinct forms of impulsivity.

Methods

Rats were trained on the five-choice serial reaction time task (5-CSRTT) of sustained visual attention and segregated according to low, mid, and high levels of motor impulsivity (LI, MI and HI, respectively), with unscreened rats used as an additional control group. A separate group of rats was trained on a delay discounting task (DDT) to assess choice impulsivity.

Results

Systemic administration of Cpd11 dose-dependently increased motor impulsivity and impaired attentional accuracy on the 5-CSRTT in all groups tested. Eticlopride selectively attenuated the increase in impulsivity induced by Cpd11, but not the accompanying attentional impairment, at doses that had no significant effect on behavioural performance when administered alone. Cpd11 also decreased choice impulsivity on the DDT (i.e. increased preference for the large, delayed reward) and decreased locomotor activity.

Conclusions

These findings demonstrate that mGluR4s, in conjunction with D₂ receptors, affect motor- and choice-based measures of impulsivity, and therefore may be novel targets to modulate impulsive behaviour associated with a number of neuropsychiatric syndromes.

SUBMITTER: Isherwood SN

PROVIDER: S-EPMC5522528 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selective and interactive effects of D<sub>2</sub> receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

Isherwood Sarah N SN Robbins Trevor W TW Nicholson Janet R JR Dalley Jeffrey W JW Pekcec Anton A

Neuropharmacology 20170506

<h4>Background</h4>Metabotropic glutamate receptor 4 (mGluR4) and dopamine D<sub>2</sub> receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D<sub>2</sub> receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-(( ...[more]

PMID: 28487067

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Project description:In general, the Hurst exponent. is used as a measure of long-term memory of time series. In previous neuroimaging studies, H has been introduced as one important parameter to define resting-state networks, reflecting upon global scale-free properties emerging from a network. H has been examined in the waiting impulsivity (WI) network in an earlier study. We found that alterations of H in the anterior cingulate cortex (H A C C ) and the nucleus accumbens (H N A c c ) were lower in high impulsive (highIMP) compared to low impulsive (lowIMP) participants. Following up on those findings, we addressed the relation between altered fractality in H A C C and H N A c c and brain activation and neural network connectivity. To do so, brain activation maps were calculated, and network connectivity was determined using the Dynamic Causal Modeling (DCM) approach. Finally, 1-H scores were determined to quantify the alterations of H. This way, the focus of the analyses was placed on the potential effects of alterations of H on neural network activation and connectivity. Correlation analyses between the alterations of H A C C /H N A c c and activation maps and DCM estimates were performed. We found that the alterations of H predominantly correlated with fronto-hippocampal pathways and correlations were significant only in highIMP subjects. For example, alterations of H A C C was associated with a decrease in neural activation in the right HC in combination with increased ACC-hippocampal connectivity. Alteration inH N A c c , in return, was related to an increase in bilateral prefrontal activation in combination with increased fronto-hippocampal connectivity. The findings, that the WI network was related to H alteration in highIMP subjects indicated that impulse control was not reduced per se but lacked consistency. Additionally, H has been used to describe long-term memory processes before, e.g., in capital markets, energy future prices, and human memory. Thus, current findings supported the relation of H toward memory processing even when further prominent cognitive functions were involved.

Dataset Information

Selective and interactive effects of D₂ receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

Background

Methods

Results

Conclusions

Publications

Selective and interactive effects of D<sub>2</sub> receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

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Background

Methods

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Selective and interactive effects of D<sub>2</sub> receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

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OmicsDI is part of the ELIXIR infrastructure

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Selective and interactive effects of D₂ receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.