Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine D1-like receptors can modulate glutamate-mediated excitatory synaptic neurotransmission, but the underlying molecular mechanism remains elusive. Here, we report that acute in-vivo morphine administration induces the long-term potentiation (Mor-LTP) of field excitatory postsynaptic potentials at the prefrontal cortex-to-nucleus accumbens shell synapses, and this process requires the activation of GluN2A-containing N-methyl-D-aspartate receptors. This Mor-LTP is completely inhibited by the D1-like receptor agonist SKF81297, but not by the D2-like receptor agonist quinpirole. SKF81297-inhibited Mor-LTP is restored by pretreatment with the TAT-conjugated interfering peptide TAT-D1-t3, which is a synthetic blocker of the direct D1-GluN2A receptor interaction. These results indicate that the activation of D1 receptors modulates Mor-LTP by the direct D1-GluN2A interaction at the prefrontal cortex-to-nucleus accumbens shell synapses and might play a role in addiction-related plastic alterations.
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PMID:Activation of the D1 receptors inhibits the long-term potentiation in vivo induced by acute morphine administration through a D1-GluN2A interaction in the nucleus accumbens. 2512 22

A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioral model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts a tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants.
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PMID:The dopamine D1-D2 receptor heteromer exerts a tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization. 2544 66