NPY mediates reward activity of morphine, via NPY Y1 receptors, in the nucleus accumbens shell

• Published in: Behavioural brain research Vol. 247; pp. 79 - 91
• Main Authors: Desai, Sagar J., Upadhya, Manoj A., Subhedar, Nishikant K., Kokare, Dadasaheb M.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.06.2013; Elsevier
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Brain stimulation reward; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Male; Morphine - pharmacology; Narcotics - pharmacology; Neuropeptide Y; Neuropeptide Y - pharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Nucleus accumbens shell; Operant conditioning chamber; Opioids; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - metabolism; Receptors, Neuropeptide - metabolism; Reward; Self Administration; Neuropeptide Y; Immunohistochemistry; Nucleus accumbens shell; Operant conditioning chamber; Brain stimulation reward; Opioids; Peptide hormone; Central nervous system; Instrumental conditioning; Morphine; Opiates; Stimulation; Basal ganglion; Narcotic analgesic; Opioid peptide; Encephalon; Learning; Nucleus accumbens; Acquisition process; Reward; Biological receptor
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2013.03.018

•While NPY potentiated, BIBP3226 attenuated reward action of morphine.•NPY, via NPY Y1 receptors, mediates morphine's reward action.•Endogenous NPYergic system in AcbSh is up regulated in self-stimulation reward.•Morphine utilize NPYergic-mesolimbic-dopaminergic circuit to produce reward. Although the interaction between endogenous neuropeptide Y (NPY) and opioidergic systems in processing of reward has been speculated, experimental evidence is lacking. We investigated the role of NPY, and its Y1 receptors, in the nucleus accumbens shell (AcbSh) in morphine induced reward and reinforcement behavior. Rats were implanted with cannulae targeted at AcbSh for drug administration, and with stimulating electrode in the medial forebrain bundle (MFB). The rats were then conditioned in an operant conditioning chamber for electrical self-stimulation of the MFB. Increased rate of lever pressings was evaluated against the frequency of the stimulating current. Increase in rate of lever presses was considered as a measure of reward and reinforcement. About 30–70% increase in self-stimulation was observed following bilateral intra-AcbSh treatment with morphine, NPY or [Leu31, Pro34]-NPY (NPY Y1/Y5 receptors agonist), however, BIBP3226 (selective NPY Y1 receptors antagonist) produced opposite effect. The reward effect of morphine was significantly potentiated by NPY or [Leu31, Pro34]-NPY, but antagonized by BIBP3226. NPY-immunoreactivity in the AcbSh, arcuate nucleus (ARC) and lateral part of bed nucleus of stria terminalis (BNSTl) was significantly more in the operant conditioned rats than in naïve control. However, morphine administration to the conditioned rats resulted in significant decrease in the NPY-immunoreactivity in all these anatomical regions. Since the role of morphine in modulation of mesolimbic-dopaminergic pathway is well established, we suggest that NPY system in AcbSh, ARC and BNSTl, perhaps acting via Y1-receptor system, may be an important component of the mesolimbic-AcbSh reward circuitry triggered by endogenous opioids.