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Aim: Our previous studies showed that exposure to acute restraint stress enhanced cocaine-induced conditioned place preference (cocaine-CPP) and suggested the possibility that co-activation of adrenergic transmission boosts the increase in medial prefrontal cortex (mPFC) neuronal activity by the activation of dopaminergic transmission. To examine this possibility, the effects of the co-treatment with dopamine (DA) and noradrenaline (NA) on mPFC neurons were compared with those of treatment with DA alone using whole-cell patch-clamp recordings., Methods: The effects of DA alone and a mixture of DA and NA on the membrane potentials and spontaneous excitatory postsynaptic currents (sEPSCs) were examined by electrophysiological recordings of mPFC pyramidal neurons in brain slices of male Sprague Dawley rats. Extracellular DA and NA levels in the mPFC during and after restraint stress exposure were also examined by in vivo microdialysis., Results: Dopamine significantly produced depolarizing effects on mPFC neurons and tended to increase sEPSC frequency. Co-administration of NA with DA produced stronger depolarizing effects and significantly increased sEPSC frequency. The findings suggest that the additional depolarizing effect of NA on DA-responsive neurons, rather than the excitation of DA-nonresponsive neurons by NA, contributes to the stronger effect of co-treatment of NA with DA., Conclusion: The present study suggests that NA released by restraint stress exposure cooperates with DA to stimulate DA-responsive neurons in the mPFC, thereby causing the stress-induced enhancement of cocaine-CPP., (© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsycho Pharmacology.)

Neurotensin receptor type-1 (Ntsr1) is the main receptor subtype that underlies neurotensin (NT)-mediated modulation of the dopamine (DA) system. Although NT and DA coexist in the basolateral nucleus of the amygdala (BLA), the function of Ntsr1 in the amygdala is not well characterized. In the present study, we utilized Ntsr1 knockout (Ntsr1-KO) mice to examine the role of Ntsr1 in the amygdala. In acute brain slices of Ntsr1-KO mice, synaptic currents elicited in BLA pyramidal neurons by electrical stimulation of the lateral nucleus of the amygdala (LA) were greatly potentiated by tetanic stimulation (BLA-long-term potentiation (LTP)). Such potentiation was not evident in pyramidal neurons of wild-type mice. In the presence of an antagonist of Ntsr1, SR48692, BLA-LTP was consistently observed in the neurons of wild-type mice, suggesting that both inherited deletion and acute pharmacological blockade of Ntsr1 induce BLA-LTP. BLA-LTP in Ntsr1-KO mice was impaired by sulpiride, a DA D2-like receptor antagonist. Conversely, quinpirole, a D2-like receptor agonist, induced pronounced BLA-LTP in wild-type mice, suggesting the upregulation of D2-like receptor activity in Ntsr1-KO mice. The ratio of NMDA receptor-mediated to non-NMDA receptor-mediated synaptic currents in Ntsr1-KO mouse BLA neurons was approximately double that measured in wild-type mouse neurons. Furthermore, quinpirole potentiated NMDA receptor-mediated synaptic currents in the BLA of wild-type mice. These results suggest that, without Ntsr1, synaptic responses from the LA to BLA pyramidal neurons undergo LTP in response to tetanus stimulation through facilitation of D2-like receptor-induced activation of NMDA receptors.Neuropsychopharmacology (2008) 33, 3135–3145; doi:10.1038/npp.2008.38; published online 19 March 2008 [ABSTRACT FROM AUTHOR]

The present study aimed to examine the rewarding effects of pain relief during the early and late stages of neuropathic pain using a conditioned place preference (CPP) test. Animal models of neuropathic pain were prepared by spinal nerve ligation in male Sprague–Dawley rats. Intraperitoneal and intrathecal injections of pregabalin (300 mg/kg and 100 μg/10 μL, respectively) suppressed allodynia in the von Frey test both 2 weeks (early stage) and 4 weeks (late stage) after nerve injury. Intraperitoneal and intrathecal injections of pregabalin induced CPP during the early stage of neuropathic pain, suggesting that the CPP test serves as an objective and quantifiable behavioral assay to assess the emotional aspect of pain relief. In contrast with the early stage of neuropathic pain, intraperitoneal or intrathecal injection of pregabalin did not induce CPP during the late stage of neuropathic pain. The extinguishment of the rewarding effects of pregabalin during the late stage of neuropathic pain is likely due to dysfunction of the mesolimbic reward system, although the possibility that neuronal mechanisms other than dysfunction of the mesolimbic reward system are involved in the extinguishment of pregabalin-induced CPP cannot be excluded. We previously reported that not only the dopamine release in the nucleus accumbens induced by intrathecal pregabalin injection but also that induced by sucrose intake were extinguished during the late stage of neuropathic pain. These findings, combined with the results of this study, suggest that pain chronification leads to dysfunction of the mesolimbic reward system. [ABSTRACT FROM AUTHOR]