Suppression of the morphine‐induced rewarding effect in the rat with neuropathic pain: implication of the reduction in µ‐opioid receptor functions in the ventral tegmental area

• Published in: Journal of neurochemistry 2002-09, Vol.82 (5), p.1192-1198
• Main Authors: Ozaki, Satoru, Narita, Minoru, Narita, Michiko, Iino, Masahiko, Sugita, Junichi, Matsumura, Yumiko, Suzuki, Tsutomu
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Binding, Competitive - drug effects; Biological and medical sciences; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Disease Models, Animal; Dopamine - analysis; Dopamine - metabolism; Dopamine - pharmacology; dopamine receptor; dopamine release; Extracellular Space - chemistry; Extracellular Space - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacokinetics; Hyperalgesia - drug therapy; Hyperalgesia - etiology; Ligation; Male; Medical sciences; Microdialysis; morphine; Morphine - pharmacology; Nervous system (semeiology, syndromes); Neurology; Nucleus Accumbens - metabolism; Pain - drug therapy; Pain - etiology; Pain Measurement - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu - metabolism; Reward; rewarding effect; sciatic nerve ligation; Sciatic Neuropathy - complications; Sciatic Neuropathy - drug therapy; Spatial Behavior - drug effects; Ventral Tegmental Area - metabolism; µ‐opioid receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.01071.x

The present study was designed to investigate the rewarding effect, G‐protein activation and dopamine (DA) release following partial sciatic nerve ligation in the rat. Here we show for the first time that morphine failed to produce a place preference in rats with nerve injury. Various studies provide arguments to support that the mesolimbic dopaminergic system, which projects from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc), is critical of the motivational effects of opioids. In the present study, there were no significant differences between sham‐operated and sciatic nerve‐ligated rats in the increases in guanosine‐5′‐o‐(3‐[35S]thio)triphosphate ([35S]GTPγS) binding to membranes of the N.Acc stimulated by either DA, the D1 receptor agonist SKF81297, the D2 receptor agonist N‐propylnoraporphine or the D3 receptor agonist 7‐hydroxy‐2‐dipropylaminotetralin (7‐OH DPAT). In contrast, the increases in [35S]GTPγS binding to membranes of the VTA induced by either morphine or a selective µ‐opioid receptor agonist [d‐Ala2, NMePhe4, Gly(ol)5]enkephalin were significantly attenuated in nerve‐ligated rats as compared with sham‐ operated rats. Furthermore, the enhancement of DA release in the N.Acc stimulated by morphine was significantly suppressed by sciatic nerve ligation. These findings suggest that attenuation of the morphine‐induced place preference under neuropathic pain may result from a decrease in the morphine‐induced DA release in the N.Acc with reduction in the µ‐opioid receptor‐mediated G‐protein activation in the VTA.