A comparison of the effects of morphine on 5-HT metabolism in the periaqueductal gray, ventromedial medulla and medullary dorsal horn: in vivo electrochemical studies in freely moving rats

Rivot, J.P.; Pointis, D.; Besson, Jean‐Marie

doi:10.1016/0006-8993(89)91227-4

Cited by 17 publications

(11 citation statements)

References 26 publications

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“…Furthermore, electrical stimulation (Bourgoin et al, 1980;Hammond et al, 1985;Sorkin et al, 1993) and microinjection of morphine (Vasko and Vogt, 1982;Vasko et al, 1984) into NRM increase the turnover or release of 5HT in the dorsal spinal cord. Moreover, it has been reported that systemic morphine increases the synthesis of spinal 5HT (Bineau-Thurotte et al, 1984; but see also and increases the concentration of 5HT metabolites in the RVM (Rivot et al, 1988(Rivot et al, , 1989), suggesting that 5HT release is increased. Selective destruction of NRM serotonergic neurons has been reported to attenuate morphine-induced antinociception significantly (Mohrland and Gebhart, 1980).…”

Section: Opioid Receptors Serotonin and Projection Neurons In The Rvmmentioning

confidence: 93%

?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

Wang

Wessendorf

1999

J. Comp. Neurol.

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The rostral ventromedial medulla (RVM) is an important mediator of the supraspinal component of opioid antinociception. Previous studies have suggested that activation of the cloned μ‐ and δ‐opioid receptors (MOR1 and DOR1 respectively) in the RVM produces the antinociception mediated by spinally projecting neurons. In the present study, we investigated the expression of mRNA encoding either MOR1 or DOR1 in the RVM of rats. In addition, we examined quantitatively the expression of MOR1 and DOR1 mRNAs in spinally projecting RVM neurons including serotonergic (5HT) cells by using in situ hybridization, immunocytochemistry, retrograde tract‐tracing, and the physical disector. Brainstem neurons were labeled in 14 male Sprague‐Dawley rats by applying Fluoro‐Gold (FG) topically to the dorsal surface of the lumbosacral spinal cord. Five‐micrometer‐thick cryostat sections were cut and in situ hybridization was performed by using full‐length cRNA probes labeled with 35S‐UTP. We found that 43% of RVM projection neurons expressed MOR1 mRNA and 83% of RVM projection neurons expressed DOR1 mRNA. Of 192 retrogradely labeled cells in the RVM, 51 cells (27%) were immunoreactive for 5HT. Of this population, half appeared to be labeled for the mRNA encoding MOR1 and over three‐fourths appeared to be labeled for the mRNA encoding DOR1. Thus, we conclude that bulbospinal neurons express MOR1 and DOR1; moreover, MOR1 and DOR1 are expressed by significant proportions of 5HT neurons projecting to or through the dorsal spinal cord. J. Comp. Neurol. 404:183–196, 1999. © 1999 Wiley‐Liss, Inc.

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Section: Opioid Receptors Serotonin and Projection Neurons In The Rvmmentioning

confidence: 93%

?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

Wang

Wessendorf

1999

J. Comp. Neurol.

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“…Some early studies suggested that morphine enhances 5-HT synthesis, release and metabolism in several brain regions (Smialowska and Bal, 1984; Spampinato et al, 1985; Rivot et al, 1989) but others have found an inhibitory effect of morphine on the firing rate of 5-HT cells in the raphe nuclei (Haigler, 1978; Alojado et al, 1994). Opioid-5-HT interactions are complex in part because different receptor subtypes mediate distinct effects on 5-HT.…”

Section: Modulation Of Serotonin Neurotransmission By Drugs Of Abusementioning

confidence: 99%

Contributions of serotonin in addiction vulnerability

2011

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The serotonin (5-hydroxytryptamine; 5-HT) system has long been associated with mood and its dysregulation implicated in the pathophysiology of mood and anxiety disorders. While modulation of 5-HT neurotransmission by drugs of abuse is also recognized, its role in drug addiction and vulnerability to drug relapse is a more recent focus of investigation. First, we review preclinical data supporting the serotonergic raphe nuclei and their forebrain projections as targets of drugs of abuse, with emphasis on the effects of psychostimulants, opioids and ethanol. Next, we examine the role of 5-HT receptors in impulsivity, a core behavior that contributes to the vulnerability to addiction and relapse. Finally, we discuss evidence for serotonergic dysregulation in comorbid mood and addictive disorders and suggest novel serotonergic targets for the treatment of addiction and the prevention of drug relapse.

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“…40,41 This hypothesis, however, contradicts cellular recordings from nucleus raphe magnus neurons, which show that activation of 5-HT-containing neurons is not necessary for morphine analgesia. 42,43 Notwithstanding the increased concentration of 5-HT metabolites in spinal and supraspinal areas consequent to systemic morphine injection, 44,45 and observations that 5-HT receptor antagonists can modulate morphine analgesia, 41 it could be that morphine affects other processes that are under the direction of the RVM, such as behavioral state, which may themselves alter central serotonergic tone. Thus, any morphine-evoked increases in 5-HT release may be secondary to primary opioid effects.…”

Section: -Ht Function In Different Pain Statesmentioning

confidence: 99%

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

2009

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Summary:The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states. There is good evidence for a prominent ␣ 2 -adrenoceptor-mediated inhibitory system and 5-HT 3 (and likely also 5-HT 2 ) serotonin receptor-mediated excitatory controls originating from brainstem and midbrain areas. The ability of cortical controls to influence spinal function allows for top-down processing through these monoamines. The links between pain and the comorbidities of sleep problems, anxiety, and depression may be due to the dual roles of noradrenaline and of 5-HT in these functions and also in pain. These controls appear, in the cases of peripheral neuropathy, spinal injury, and cancer-induced bone pain to be driven by altered peripheral and spinal neuronal processes; in opioid-induced hyperalgesia, however, the same changes occur without any pathophysiological peripheral process. Thus, in generalized pain states in which fatigue, mood changes, and diffuse pain occur, such as fibromyalgia and irritable bowel syndrome, one could suggest an abnormal engagement of descending facilitations with or without reduced inhibitions but with central origins. This would be an endogenous central malfunction of top-down processing, with the altered monoamine systems underlying the observed symptoms. A number of analgesic drugs can either interact with or have their actions modulated by these descending systems, reinforcing their importance in the establishment of pain but also in its control. Key Words: 5-HT receptors, 5-HT, serotonin, noradrenaline, RVM, rostral ventromedial medulla, opioidinduced hyperalgesia, neuropathy, fibromyalgia. PAIN, COMORBIDITIES, AND MONOAMINESPain and mood share certain neurological pathways in the CNS and have overlapping neurochemical bases, in particular their modulation by monoamine systems. This provides the substrate through which pain can influence mood, giving rise to comorbidities or secondary symptoms such as anxiety and depression, 1,2 and by the same continuum allows mood to exacerbate pain; indeed, patients with depression often present with symptoms that include medically unexplained pain, with the mean prevalence of such occurrence cited as 65%.1,3 Emotional facets of nociception play a significant role in the pain experience, with fear largely driving adaptive behaviors that enable avoidance of actual or impending harm. This therefore subserves the key function of pain, to protect the integrity and survival of an organism. Moreover, the role of emotions and state of mind in pain partly underlie the variable relationship between the intensity of damaging stimuli and perceived pain, such that at any given time and for any given nociceptive stimulus, painful response can be influenced by emotional state (the psychological context in which the stimulus is received), emotional trait (the psychological characteristics of the recipient), and cognitive set (attention and vigilance, for example).Depression is associated with abnormalities in the monoaminergic ...

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A comparison of the effects of morphine on 5-HT metabolism in the periaqueductal gray, ventromedial medulla and medullary dorsal horn: in vivo electrochemical studies in freely moving rats

Cited by 17 publications

References 26 publications

?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

Contributions of serotonin in addiction vulnerability

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

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