Ontogeny and distribution of opioid receptors in the rat brainstem

Xia, Ying; Haddad, Gabriel G.

doi:10.1016/0006-8993(91)90457-7

Cited by 156 publications

(91 citation statements)

References 55 publications

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“…Although the present study focused exclusively on MOR, it is possible that other opioid receptors are also involved in the sex-induced activation of the mesolimbic system. Autoradiographic studies show that delta and kappa opioid receptors are present in the VTA, albeit at much lower densities compared to MOR (Mansour et al, 1987(Mansour et al, , 1988Dilts and Kalivas, 1990;Xia and Haddad, 1991). Furthermore, delta agonists infused into the VTA are 100-1000 times less potent at stimulating DA release in the NAc, while kappa agonists fail to do so altogether (Devine et al, 1993), suggesting that sex-induced activation of the mesolimbic DA pathway occurs primarily via MOR activation.…”

Section: Discussionmentioning

confidence: 99%

Sexual Behavior and Sex-Associated Environmental Cues Activate the Mesolimbic System in Male Rats

Balfour

Coolen

2003

Neuropsychopharmacol

165

125

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The mesolimbic system plays an important role in the regulation of both pathological behaviors such as drug addiction and normal motivated behaviors such as sexual behavior. The present study investigated the mechanism by which this system is endogenously activated during sexual behavior. Specifically, the effects of sexual experience and sex-related environmental cues on the activation of several components of the mesolimbic system were studied. The mesolimbic system consists of a dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Previous studies suggest that these neurons are under tonic inhibition by local GABA interneurons, which are in turn modulated by mu opioid receptor (MOR) ligands. To test the hypothesis that opioids are acting in the VTA during sexual behavior, visualization of MOR internalization in VTA was used as a marker for ligand-induced activation of the receptor. Significant increases in MOR internalization were observed following copulation or exposure to sex-related environmental cues. The next goal was to determine if sexual behavior activates dopamine neurons in the VTA, using tyrosine hydroxylase as a marker for dopaminergic neurons and Fos-immunoreactivity as a marker for neuronal activation. Significant increases in the percentage of activated dopaminergic neurons were observed following copulation or exposure to sex-related environmental cues. In addition, mating and sex-related cues activated a large population of nondopaminergic neurons in VTA as well as neurons in both the NAc Core and Shell. Taken together, our results provide functional neuroanatomical evidence that the mesolimbic system is activated by both sexual behavior and exposure to sex-related environmental cues.

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Section: Discussionmentioning

confidence: 99%

Sexual Behavior and Sex-Associated Environmental Cues Activate the Mesolimbic System in Male Rats

Balfour

Coolen

2003

Neuropsychopharmacol

165

125

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“…DOR Function Is Critical for HPC-induced Neuroprotection-The DOR is highly expressed in the cortex (22,24) and is…”

Section: Hpc-induced Neuroprotection Is Dependent On the Durationmentioning

confidence: 99%

“…Because it is impractical to analyze molecular mechanisms by administering multiple drugs to live animals, we performed this study on neurons in culture and specifically focused on cortical neurons, since we have previously shown that the cortex has the highest DOR density (22,24).…”

mentioning

confidence: 99%

Oxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals

Chieh

Qian

Ghassemi

et al. 2005

Journal of Biological Chemistry

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150

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The detrimental effect of severe hypoxia (SH) on neurons can be mitigated by hypoxic preconditioning (HPC), but the molecular mechanisms involved remain unclear, and an understanding of these may provide novel solutions for hypoxic/ischemic disorders (e.g. stroke). Here, we show that the ␦-opioid receptor (DOR), an oxygen-sensitive membrane protein, mediates the HPC protection through specific signaling pathways. Although SH caused a decrease in DOR expression and neuronal injury, HPC induced an increase in DOR mRNA and protein levels and reversed the reduction in levels of the endogenous DOR peptide, leucine enkephalin, normally seen during SH, thus protecting the neurons from SH insult. The HPC-induced protection could be blocked by DOR antagonists. The DOR-mediated HPC protection depended on an increase in ERK and Bcl 2 activity, which counteracted the SH-induced increase in p38 MAPK activities and cytochrome c release. The cross-talk between ERK and p38 MAPKs displays a "yinyang" antagonism under the control of the DOR-G protein-protein kinase C pathway. Our findings demonstrate a novel mechanism of HPC neuroprotection (i.e. the intracellular up-regulation of DOR-regulated survival signals).Neuronal death as a result of neuronal injury following hypoxic/ischemic insults, such as stroke, is an irreversible process that leads to long term neurological deficit. The prevention of neuronal injury is therefore critical in rescuing the brain from neurological disaster. However, clinical strategies that may help mitigate the effects of hypoxic/ischemic injury are still very limited.One strategy that has been shown to provide effective protection from harmful stress is known as preconditioning. This involves transient, but sublethal, exposure to a stress, resulting in enhanced cellular resistance to subsequent severe stress. It was initially demonstrated in the heart (1) and subsequently found to work in other organ beds (2). The effects of preconditioning have been widely studied in the whole brain (3, 4), as well as in vitro in brain slices (5, 6) and neuronal cultures (7-9). Most studies to date have shown the beneficial effects of preconditioning on rescuing neurons from cell injury in response to subsequent severe insults. Hypoxic preconditioning (HPC), 1 for example, caused by lowering the oxygen content or by combined oxygen and glucose deprivation, protects against subsequent hypoxic injury (4,7,8,10). However, a recent study failed to show neuronal protection with HPC treatment (11), suggesting that the neuronal response to preconditioning may vary depending on neuronal situation and involve complex mechanisms. These molecular mechanisms remain unclear, especially with regard to intracellular signal transduction. In this study, we demonstrated that, in neurons in culture, HPCinduced neuroprotection is dependent on specific factors and that the effect is mediated by intracellular up-regulation of ␦-opioid receptor (DOR)-regulated survival signals, which suppress the increased activity of intracellular death s...

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“…The mechanism underlying the age-difference is unclear at this point. It may be partially related to the differential expression of membrane proteins (e.g., NMDA receptors and DOR) and intracellular components of signal transduction during neuronal development (Xia and Haddad, 1991;Zhang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK

et al. 2007

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MAP kinase is associated with delta-opioid receptor (DOR) signaling and plays a role in cell survival/ death. Since anisomycin may alter MAP kinase activity and affect neuronal survival, we investigated whether anisomycin alters neuronal response to hypoxic stress and DOR inhibition. The experiments were performed in cultured cortical neurons. MAP kinase activities were determined by immunoblotting and neuronal viability was assessed by LDH leakage and live/dead morphological study. DOR inhibition with naltrindole (10 μM) led to significant injury in normoxic neurons after 24 hours of treatment and exacerbated hypoxia-induced injury. Along with the injury, either by hypoxia or naltrindole, phosphorylated p38 increased in a major way, while phosphorylated ERK and JNK had no significant change or slightly decreased. Anisomycin (50 ng/ml) prevented the increase in phosphorylated p38 immunoreactivity induced by naltrindole and reduced the neuronal injury. The results suggest that 1) MAP kinases are differentially involved in neuronal response to hypoxia and DOR inhibition in cortical neurons with phosphorylated p38 immunoreactivity being up-regulated and 2) Anisomycin attenuates the increase in phosphorylated p38 immunoreactivity and reduces neuronal injury induced by hypoxia-and DOR inhibition.

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Ontogeny and distribution of opioid receptors in the rat brainstem

Cited by 156 publications

References 55 publications

Sexual Behavior and Sex-Associated Environmental Cues Activate the Mesolimbic System in Male Rats

Sexual Behavior and Sex-Associated Environmental Cues Activate the Mesolimbic System in Male Rats

Oxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals

Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK

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