Regulation of neurotransmitter interactions in the ventral striatum.
Transsynaptic activation of neuronal circuits originating in the basal forebrain contributes to psychostimulant-evoked dopamine and glutamate release and consequent changes in medium spiny neuronal gene expression in the ventral striatum. New evidence from microdialysis studies indicates that amphetamine-induced dopamine and glutamate release in vivo is partially calcium dependent. The calcium-dependent component is totally blocked by a kappa opioid receptor agonist, indicating that endogenous opioids may regulate dopamine-glutamate interactions in the ventral striatum. Further, muscarinic receptor blockade increases, and muscarinic receptor stimulation decreases, dialysate glutamate levels in the striatum. Pre- and postsynaptic muscarinic receptors contribute to the ability of the muscarinic antagonist, scopolamine, to augment D1 receptor-stimulated immediate early and neuropeptide gene expression. Moreover, scopolamine prevents a D2 antagonist from blocking D1 agonist-induced gene expression, indicating that activation of cholinergic interneurons contributes to D1/D2 interactions in the striatum. Thus, transsynaptic activity and presynaptic muscarinic and kappa opioid receptors regulate dopamine and glutamate interactions that switch on and off multiple intracellular signaling cascades. Changes in immediate early and neuropeptide gene expression that result from activation of these cascades are mediated by such nuclear transcription factors as phosphorylated cyclase response element-binding protein. In addition, a novel signaling pathway involving the RAR/RXR nuclear hormone receptor complex is implicated in the control of dopamine receptor and neuropeptide gene expression in the striatum.
Department of Anatomy and Cell Biology, East Carolina University, School of Medicine, Greenville, North Carolina 27858-4354, USA. mcginty@brody.med.ecu.edu
J F
JF
McGinty
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006706:Homeostasis; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology*; D017982:Receptors, Biogenic Amine / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology; D013569:Synapses / Q000502:physiology
D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D017982:Receptors, Biogenic Amine; D017473:Receptors, Opioid, kappa