Cross interaction of melanocortinergic and dopaminergic systems in neural modulation

Abstract

Melanocortinergic and dopaminergic systems are widely distributed in the CNS and have been established as a crucial regulatory component in diverse physiological functions. The pharmacology of both melanocortinergic and dopaminergic systems including their individual receptors, signaling mechanisms, agonists and antagonists has been extensively studied. Several lines of evidence showed that there existed a cross interaction between the receptors of melanocortinergic and dopaminergic systems. The data available at present had expanded our understanding of melanocortinergic and dopaminergic system interaction in neural modulation, which will be main discussed in this paper.

Keywords: Melanocortinergic system; dopamine; dopaminergic system; receptor.

Figure 1

Summary diagram showed that the sympathetic and motor pathway between the several CNS nuclei and skeletal muscle. Left (blue line): As an important part of the reward pathway, the major dopaminergic pathways are involved in the VTA, NAc and the prefrontal cortex. Injection of recombinant PRV-614 expressing red fluorescence protein (RFP) into the gastrocnemius muscle resulted in retrograde infection of the ipsilateral intermediolateral nucleus (IML) of spinal segments, VTA, nucleus accumbens and the prefrontal cortex neurons in spinally transected transgenic MC4R-GFP mice; PRV-614/MC4R-GFP neurons were detected in the VTA, nucleus accumbens and the prefrontal cortex, suggesting that the VTA, nucleus accumbens and the prefrontal cortex may play an important role in the sympathetic pathway by the melanocortinergic signaling. Right (green line): Dopaminergic motor functions are linked to a separate pathway, and the major dopaminergic motor pathways are involved in the substantia nigra and the striatum. PRV-614 was injected into the gastrocnemius muscle of surgically sympathectomized transgenic MC4R-GFP mice as a specific transsynaptic retrograde tracer. After 3, 4, 5 or 6 days, spinal cord and brain were collected for immunofluorescence staining. The temporal order of PRV-614 labeled neurons was found in the ventral horn (VH) motor neurons of spinal segments on day 3; pedunculopontine tegmental nucleus (PPTg) and substantia nigra on day 4-5; and the dorsal striatum (caudate and putamen) on day 5-6. We found that PRV-614/MC4R-GFP double-labeled neurons in the VH, PPTg, substantia nigra and the dorsal striatum, suggesting that the PPTg, substantia nigra and the dorsal striatum may play a major role in the initiation of skeletal muscle tone by the melanocortinergic and catecholaminergic pathway. Some drawings were taken from Qing-Xiong Hong (Epilepsy & Behavior 2014) and Hong-Bing Xiang (Brain 2013).