Evidence that 5‐hydroxytryptamine in the forebrain is involved in naloxone‐precipitated jumping in morphine‐dependent rats

Cervo, Luigi; Romandini, S.; Samanin, R.

doi:10.1111/j.1476-5381.1983.tb10546.x

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…Moreover, the behavior of recombinant mice lacking 5-HT and dopamine reuptake transporters or 5-HT 1B receptors suggests that 5-HT interacts with dopamine in the NAcc to influence drug self-administration (Rocha et al, 1998;Uhl et al, 2002). Both the reinforcing property of morphine and withdrawal syndrome are affected by 5-HT receptor ligands, supporting the hypothesis that 5-HT plays a role in opiate addiction (Cervo et al, 1983;Carboni et al, 1989;Harris and Aston-Jones, 2001). …”

mentioning

confidence: 64%

GABAergic and Glutamatergic Afferents in the Dorsal Raphe Nucleus Mediate Morphine-Induced Increases in Serotonin Efflux in the Rat Central Nervous System

Tao¹,

Auerbach²

2002

The Journal of Pharmacology and Experimental Therapeutics

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To characterize the effects of morphine on serotonin (5-HT) in the central nervous system, we used microdialysis in freely behaving rats. Subcutaneous injection of morphine sulfate produced a dose-dependent increase in extracellular 5-HT in the dorsal raphe nucleus (DRN) and a forebrain site, the nucleus accumbens (NAcc). To determine the site of action for this effect, the opioid receptor antagonist naltrexone was infused into either the DRN or NAcc. Naltrexone infusion (300 M) into the DRN but not the NAcc attenuated the increase in 5-HT elicited by systemic morphine (20 mg/kg). This suggests that morphine acts in the DRN to alter the activity of 5-HT neurons that project to NAcc. Consistent with this conclusion, infusion of the GABA A receptor antagonist bicuculline (100 M) into the DRN but not the NAcc also blocked the effect of systemic morphine. Similarly, the effect of systemic morphine was blocked by infusion into the DRN of the GABA A receptor agonist muscimol (30 M) and attenuated by the GABA B receptor agonist (Ϯ)-baclofen (100 M). This provides evidence that morphine indirectly influences 5-HT release via opioid receptors on GABAergic neurons in the DRN. A new finding is that ionotropic glutamate receptor antagonists [kynurenate or a mixture of (Ϯ)-2-amino-5-phosphonopentanoic acid and 6,7-dinitro-quinoxaline-2,3-dione] infused in the DRN also attenuated the effect of systemic morphine. These results suggest that morphine acts on GABAergic and glutamatergic afferents to indirectly influence the activity of 5-HT neurons in the DRN. Understanding the details of this neural circuitry may provide new leads for treatment of opiate addiction.

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confidence: 64%

GABAergic and Glutamatergic Afferents in the Dorsal Raphe Nucleus Mediate Morphine-Induced Increases in Serotonin Efflux in the Rat Central Nervous System

Tao¹,

Auerbach²

2002

The Journal of Pharmacology and Experimental Therapeutics

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“…In addition, double dopamine/5-HT transporter knockout mice fail to show cocaine CPP (Sora et al 2001), indicating a role for 5-HT as well as dopamine in psychostimulant reward. The 5-HT system has also been shown to be involved in both euphoric effects of opioids (Carboni et al 1989; Carboni et al 1988; Carboni et al 1989; Glick and Cox, 1977; Alaei et al 2002) and the dysphoric responses that are part of the withdrawal syndrome (Cervo et al 1983; Harris and Aston-Jones, 2001; Goeldner et al 2011; Cervo et al 1981). There is also a high degree of comorbidity of affective disorders such as major depression with opiate dependence (Brooner et al 1997; Mason et al 1998; Pani et al 1997; Rounsaville et al 1982; Woody et al 1975).…”

Section: Introductionmentioning

confidence: 99%

Morphine history sensitizes postsynaptic GABA receptors on dorsal raphe serotonin neurons in a stress-induced relapse model in rats

Staub

Lunden

Cathel

et al. 2012

Psychoneuroendocrinology

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The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Previous work has shown that the dorsal raphe nucleus (DR)-5-HT system is inhibited by swim stress via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor (CRF). Additionally, the DR 5-HT system is regulated by opioids. The present study tests the hypothesis that the DR 5-HT system regulates stress-induced opioid relapse. In the first experiment, electrophysiological recordings of GABA synaptic activity in 5-HT DR neurons were conducted in brain slices from Sprague-Dawley rats that were exposed to swim stress-induced reinstatement of previously extinguished morphine conditioned place preference (CPP). Behavioral data indicate that swim stress triggers reinstatement of morphine CPP. Electrophysiology data indicate that 5-HT neurons in the morphine-conditioned group exposed to stress had increased amplitude of inhibitory postsynaptic currents (IPSCs), which would indicate greater postsynaptic GABA receptor density and/or sensitivity, compared to saline-controls exposed to stress. In the second experiment, rats were exposed to either morphine or saline CPP and extinction, and then 5-HT DR neurons from both groups were examined for sensitivity to CRF in vitro. CRF induced a greater inward current in 5-HT neurons from morphine-conditioned subjects compared to saline-conditioned subjects. These data indicate that morphine history sensitizes 5-HT DR neurons to the GABAergic inhibitory effects of stress as well as to some of the effects of CRF. These mechanisms may sensitize subjects with a morphine history to the dysphoric effects of stressors and ultimately confer an enhanced vulnerability to stress-induced opioid relapse.

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“…Thus, 5-HT has been hypothesized to be one of the factors involved in the changes in physiology and behavioral state which occur during opiate withdrawal. However, several findings have suggested that 5-HT is not responsible for the physical symptoms of withdrawal (Blasig et al, 1976;Silverstone et al, 1993), except for a possible role in jumping behavior (Cervo et al, 1983;Way et al, 1968). For example, it has been shown that serotonergic transmission blockade, either by specific 5-HT lesion (Ho et al, 1972) or a 5-HT antagonist (Cervo et al, 1981;Samanin et al, 1980) along with chronic morphine treatment, reduces the development of jumping behavior during morphine withdrawal.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of 5-HT Neurotransmission Increases Clonidine Protective Effects on Naloxone-induced Conditioned Place Aversion in Morphine-dependent Rats

Caillé

Stinus

Fernández-Espejo

et al. 2002

Neuropsychopharmacol

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Previous pharmacological studies have implicated serotonergic brain systems in opiate-withdrawal-precipitated conditioned place aversion. To assess this hypothesis, we tested the effects of either (i) a near-total 5,7-dihydroxytryptamine-induced lesion (90% depletion) or (ii) an acute serotonin (5-HT) inhibition induced by the specific stimulation of 5-HT1A autoreceptors (8-OHDPAT 5-100 mg/kg), on naloxone-induced conditioned place aversion in morphine-dependent rats. Morphine dependence was induced by the implantation of morphine slow-release pellets. The protective properties of clonidine (an alpha-2 adrenergic agonist classically given for opiate detoxification) were also tested after inhibition of 5-HT transmission. Serotonergic lesions in morphine-dependent rats failed to alter naloxone-induced conditioned place aversion but increased the sensitivity to the protective effects of clonidine. Acute neuropharmacological blockade of serotonin transmission also potentiated the clonidine effects on naloxone-induced conditioned place aversion. When combined with the 5-HT1A agonist 8-OHDPAT, clonidine was also found to be more potent. Further understanding of this serotonin/noradrenaline interaction might help devise new therapeutic treatments for the acute opiate withdrawal syndrome.

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Evidence that 5‐hydroxytryptamine in the forebrain is involved in naloxone‐precipitated jumping in morphine‐dependent rats

Cited by 10 publications

References 15 publications

GABAergic and Glutamatergic Afferents in the Dorsal Raphe Nucleus Mediate Morphine-Induced Increases in Serotonin Efflux in the Rat Central Nervous System

GABAergic and Glutamatergic Afferents in the Dorsal Raphe Nucleus Mediate Morphine-Induced Increases in Serotonin Efflux in the Rat Central Nervous System

Morphine history sensitizes postsynaptic GABA receptors on dorsal raphe serotonin neurons in a stress-induced relapse model in rats

Inhibition of 5-HT Neurotransmission Increases Clonidine Protective Effects on Naloxone-induced Conditioned Place Aversion in Morphine-dependent Rats

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