Changes in Brain Dopamine Metabolism During Withdrawal from Chronic Oral Self-administration of Morphine, and in Response to a Morphine Challenge in the Withdrawn State

Ahtee, Liisa; Attila, L. M. J.; Carlson, K. R.; Haikala, Heimo

doi:10.1007/978-1-349-10047-7_44

Cited by 31 publications

(18 citation statements)

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“…Reduced plasma insulin and leptin concentrations also suggest increased sympathetic activity in morphine-treated rats (Bartness, 1998;Rayner and Trayhurn, 2001). In support of this, previous studies have shown that opioid dependence and withdrawal are associated with increased noradrenergic and catecholaminergic activity in brain and hypothalamus (Ahtee et al, 1989;Fuertes et al, 2000;Milanes et al, 1993Milanes et al, , 1997Milanes et al, , 1998.…”

Section: Energy Balancesupporting

confidence: 58%

Intermittent Morphine Administration Induces Dependence and is a Chronic Stressor in Rats

Houshyar

Gómez

Manalo

et al. 2003

Neuropsychopharmacol

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Although constant treatment with morphine (implanted pellets) does not activate the hypothalamic-pituitary-adrenal (HPA) axis, intermittent injections of morphine may constitute a chronic stressor in rats. To test this hypothesis, we compared the effects of morphine in escalating doses (10-40 mg/kg, s.c.) or saline injected twice daily for 4 days on energy balance, hormones, HPA responses to novel restraint and central corticotropin-releasing factor (CRF) mRNA 12 h and 8 days after the last morphine injection in adult male Sprague-Dawley rats. Weight gain stopped at the onset of morphine, weight loss was marked 36 h postmorphine; thereafter, body weight gain paralleled saline controls. At 12 h, insulin, leptin, and testosterone concentrations were reduced but normalized by 8 days. Restraint and tail nicks caused facilitated ACTH responses at 12 h, under-responsiveness at 8 days. CRF mRNA, measured only at 12 h, was increased in the paraventricular (PVN) and Barrington's nuclei (BAR), decreased in the bed nuclei of the stria terminalis (BNST) and unchanged in the amygdala (CeA) in morphine-treated rats. After stress, CRF mRNA increased in PVN in both groups, increased in BAR and decreased in BNST in saline but not morphine groups, and was unchanged in CeA in both groups. Results from all variables characterize intermittent morphine injections as a chronic stressor. In contrast to constant treatment, injected morphine probably allows some withdrawal during each 12 h interval, causing repeated stress. Drug addicts treat themselves intermittently, and stress causes relapse after withdrawal. Thus, intermittent morphine, itself, may promote relapse.

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Section: Energy Balancesupporting

confidence: 58%

Intermittent Morphine Administration Induces Dependence and is a Chronic Stressor in Rats

Houshyar

Gómez

Manalo

et al. 2003

Neuropsychopharmacol

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“…In response to a longlasting overstimulation of dopaminergic neurons, the normal function of the system seems to become dependent on the presence of the exogenous substance. Drug abstinence, therefore, might result in understimulation of dopaminergic neurons followed by a relative lack of DA in the mesolimbic system, thus producing emotional withdrawal symptoms such as dysphoria and anhedonia in both animal models and humans (Acquas and Di Chiara, 1992;Ahtee et al, 1989;Volkow et al, 2002). So far, there is no satisfactory therapy for this anhedonic emotional state which has an enormous influence on the outcome of clinical treatment of addiction, leading to relapse in a large number of patients (Mattick et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Repetitive Transcranial Magnetic Stimulation Increases the Release of Dopamine in the Nucleus Accumbens Shell of Morphine-Sensitized Rats During Abstinence

Erhardt

Sillaber

Welt

et al. 2004

Neuropsychopharmacol

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Recent studies in rodents have shown that withdrawal from chronic drug abuse is associated with a significant decrease in dopamine (DA) release in mesolimbic structures, especially in the shell region of the nucleus accumbens. Since the DA system is known to play an important role in reward processes, a withdrawal-associated impairment in mesolimbic DA-mediated transmission could possibly implicate reward deficit and thus enhance vulnerability to drug craving and relapse. We have previously demonstrated that acute repetitive transcranial magnetic stimulation (rTMS) has a modulatory effect on DA release in several areas of the rat brain, including dorsal striatum, hippocampus, and nucleus accumbens shell. In the present study, we investigated the possible use of rTMS as a tool in reestablishing the dysregulated DA secretion observed during withdrawal in morphine-sensitized male Sprague-Dawley rats. Using intracerebral microdialysis, we monitored the effects of acute rTMS (20 Hz) on the intra-accumbal release-patterns of DA in freely moving animals that were subjected to a morphine sensitization scheme for a period of 8 days. We provide first evidence that acute rTMS (20 Hz) is able to increase DA concentration in the shell region of the nucleus accumbens in both control animals and morphinesensitized rats during abstinence. The DA release in morphine-sensitized rats was significantly higher than in controls. rTMS, therefore, might gain a potential therapeutic role in the treatment of dysphoric and anhedonic states during drug withdrawal in humans.

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“…The stereotypies induced by morphine and other m-opioids in rats treated repeatedly with opioids have been linked to the activation of the striatal dopaminergic system (Morelli et al, 1989). Indeed, we have shown that the e ect of morphine on striatal DA transmission is augmented during withdrawal from chronic morphine treatment (Ahtee et al, 1989;Attila & Ahtee, 1984;Honkanen et al, 1994). Therefore, we investigated whether tolerance develops to the inhibitory component of morphine on striatal DA release, which in turn might contribute to the sensitization of DA release in the withdrawal from repeated opioid treatment.…”

Section: Introductionmentioning

confidence: 70%

“…Some previous studies showed that acute systemic administration of opioids did not increase the release of nigrostriatal DA (Ahtee et al, 1989;Wood & Rao, 1991;Wood & Richard, 1982;Wood et al, 1980;Yonehara & Clouet, 1984). Also, in studies in which DA release was measured from striatal slices, it has been shown that m-opioids somewhat retard the release of DA (Celsen & Kuschinsky, 1974;Kuschinsky et al, 1975;Loh et al, 1976;Schlosser et al, 1995;Widdowson & Holman, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…However, contrary to the increase of the acidic DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) we have repeatedly found that the post-mortem concentration of 3-methoxytyramine (3-MT), a metabolite considered to re¯ect the release of DA (for a review see Wood & Altar, 1988) tends to decrease in the striatum of rats or mice given relatively large doses of morphine (Ahtee et al, 1989;Airio & Ahtee, 1997). Morphine (Celsen & Kuschinsky, 1974;Kuschinsky et al, 1975;Marien et al, 1983;Westfall et al, 1983) and the selective m-receptor agonist [DAla 2 , MePhe 4 , Gly-ol 5 ]enkephalin (DAMGO) (Widdowson & Holman, 1992) have been found to decrease the stimulated release of DA from striatal slices as well.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration

Piepponen

Mikkola

Ruotsalainen

et al. 1999

British J Pharmacology

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1 The e ect of intrastriatally-administered morphine on striatal dopamine (DA) release was studied in freely moving rats. Morphine (1, 10 or 100 mM) was given into the striatum by reversed microdialysis, and concentrations of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously measured from the striatal dialysates. 2 Intrastriatally-administered morphine signi®cantly and dose-dependently decreased the extracellular concentration of DA, the concentrations of the acidic DA metabolites were only slightly decreased. The e ect of morphine was antagonized by naltrexone (2.25 mg kg 71 , s.c.). Pretreatment with a preferential k-opioid receptor antagonist, MR2266 [(7)-5,9 alpha-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphane; 1 mg kg 71 , s.c.], had no e ect on the decrease of extracellular DA evoked by intrastriatal morphine (100 mM). 3 Intrastriatal administration of the selective m-opioid receptor agonist [D-Ala 2 ,MePhe 4 ,Gly-ol 5 ] enkephalin (DAMGO; 1 mM), signi®cantly decreased the extracellular concentration of DA in the striatum. 4 When the rats were given morphine repeatedly in increasing doses (10 ± 25 mg kg 71 , s.c.) twice daily for 7 days and withdrawn for 48 h, the decrease of extracellular DA induced by morphine (100 mM) was signi®cantly less than that seen in saline-treated controls. 5 Our results show that besides the well-known stimulatory e ect there is a local inhibitory component in the action of morphine on striatal DA release in the terminal regions of nigrostriatal DA neurones. Tolerance develops to this inhibitory e ect during repeated morphine treatment. Furthermore, our results suggest that the e ect of intrastriatally-administered morphine is mediated by the m-opioid receptors.

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Changes in Brain Dopamine Metabolism During Withdrawal from Chronic Oral Self-administration of Morphine, and in Response to a Morphine Challenge in the Withdrawn State

Cited by 31 publications

References 0 publications

Intermittent Morphine Administration Induces Dependence and is a Chronic Stressor in Rats

Intermittent Morphine Administration Induces Dependence and is a Chronic Stressor in Rats

Repetitive Transcranial Magnetic Stimulation Increases the Release of Dopamine in the Nucleus Accumbens Shell of Morphine-Sensitized Rats During Abstinence

Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration

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