Selective and interactive effects of D 2 receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity
| Autor: | Anton Pekcec, Trevor W. Robbins, Sarah N. Isherwood, Janet R. Nicholson, Jeffrey W. Dalley |
|---|---|
| Přispěvatelé: | Robbins, Trevor [0000-0003-0642-5977], Dalley, Jeffrey [0000-0002-2282-3660], Apollo - University of Cambridge Repository |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine GP globus pallidus Dopamine IPSC inhibitory post-synaptic current Receptors Metabotropic Glutamate CSF cerebrospinal fluid SD stimulus duration 0302 clinical medicine Salicylamides DDT delay discounting task Cyclic AMP Excitatory Amino Acid Agonists Attention LH limited hold mGluR4 3. Good health cAMP cyclic adenosine monophosphate Dopamine D2 Receptor Antagonists Delay Discounting Interactive effects Visual Perception Glutamate medicine.symptom Psychology Social psychology medicine.medical_specialty ITI inter-trial interval MI mid-impulsive Eticlopride hydrochloride (PubChem CID: 6917728) Motor Activity Impulsivity Article Indirect pathway Styrenes Striatum LI low-impulsive 03 medical and health sciences Cellular and Molecular Neuroscience mGluR metabotropic glutamate receptor medicine Animals Psychiatry EC30 effective concentration at 30% EC50 effective concentration at 50% D2 receptors Pharmacology Psychotropic Drugs Dose-Response Relationship Drug Receptors Dopamine D2 TO timeout Rats Pyrimidines 030104 developmental biology MSN medium spiny neuron D(2) receptors HI high-impulsive GABA gamma-aminobutyric acid Impulsive Behavior 5-CSRTT five-choice serial reaction time task d-Amphetamine (PubChem CID: 5826) STN subthalamic nucleus 030217 neurology & neurosurgery EPSC excitatory post-synaptic current |
| Zdroj: | Neuropharmacology |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2017.05.006 |
| Popis: | 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. Highlights • Positive allosteric mGluR4 modulation increases motor impulsivity and impairs aspects of visual attention. • Positive allosteric mGluR4 modulation decreases choice impulsivity as well as indices of motor function. • Blocking D2 receptors selectively attenuates the effect of positive allosteric mGluR4 modulation on motor impulsivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect