Glutamate Sample Clauses

Glutamate. It has become increasingly evident that in addition to dopamine, glutamate plays an essential role in drug reward and reinforcement. Dopaminergic neurons in the NAc and VTA receive extensive glutamatergic input from the PFC, amygdala and hippocampus 48,112,215,256,264,343,654. Cocaine and amphetamine both stimulate glutamate release in the PFC and NAc 540 which is potentiated with repeated exposure 539. Glutamate enhances dopaminergic transmission by increasing activ- ity of the dopaminergic neurons in the VTA, and facilitating dopamine release from the presynaptic terminals in the NAc 48,215,335,654. Many of the actions of the excitatory transmitter rely on this stimulatory interaction with the dopamine system. For example, basal and psychostimulant-induced locomotion, which are critically dependent on dopamine, are stimulated and inhibited by glutamatergic agonists and antagonists, respectively 534,650. However, as described below, some of the actions of the excitatory transmitter in psychostimulant reinforcement are independent of dopamine. Glutamate acts via two classes of receptors: ionotropic (ligand-gated ion ▇▇▇▇- ▇▇▇▇) and metabotropic (G-protein coupled) receptors, each consisting of multiple subtypes that may, depending on localisation and function, have distinct roles in drug reinforcement. During maintenance of cocaine self-administration, stimula- tion of ionotropic glutamate receptors in the NAc causes a leftward shift in the dose-response curve, whereas antagonism of these receptors is ineffective 128. The authors argue that signalling via ionotropic receptors in the NAc enhances cocaine reward whereas it is not required for maintenance of cocaine self-administration. Conversely, blockade of the metabotropic glutamate receptor 5 (mGluR5) reduces cocaine-maintained self-administration and the motivation to obtain the drug under a progressive ratio schedule, while elevating reward thresholds for intracranial self- stimulation 350,380,495,658. Furthermore, mice lacking the mGluR5 do not self-administer cocaine and do not show increased locomotion after cocaine administration, de- spite the fact that dopamine function is comparable to that of wild-type mice 105. These studies point to an important role for mGluR5 in cocaine reward, which may be independent of dopamine transmission. Glutamatergic transmission via ionotropic and metabotropic receptors modulates drug- and cue-induced reinstatement of cocaine seeking which is in good agree- ment wi...

Glutamate. This is the primary excitatory neurotransmitter in the brain. There are several types of ionotropic glutamate receptors, classified as NMDA (N-methyl-D-aspartate) and non- NMDA receptors (AMPA and Kainate). AMPA and kainate are permeable to sodium ions and mediate fast excitatory neuronal signalling. NMDA is only activated during prolonged depolarisation. The only medication currently with selective effects on glutamate is perampanel, which is an AMPA receptor antagonist. Blockade of the NMDA subtype of glutamate receptor is also believed to partly contribute to the pharmacological profile of felbamate and topiramate.