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Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal.

ABSTRACT: Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST). We compared dopamine transients in the NAc with norepinephrine concentration changes in the vBNST, and correlated release with specific withdrawal-related behaviors. Morphine increased dopamine transients in the NAc, but did not elicit norepinephrine responses in the vBNST. Conversely, dopamine output was decreased during withdrawal, while norepinephrine was released in the vBNST during specific withdrawal symptoms. Both norepinephrine and withdrawal symptoms could be elicited in the absence of morphine by administering naloxone with an ?₂ antagonist. The data support reciprocal roles for dopamine and norepinephrine signaling during drug exposure and withdrawal. The data also support the allostasis model and show that negative-reinforcement may begin working after a single exposure/withdrawal episode.

SUBMITTER: Fox ME

PROVIDER: S-EPMC5240169 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal.

Fox Megan E ME Rodeberg Nathan T NT Wightman R Mark RM

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160727 3

Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycl ...[more]

PMID: 27461081

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Project description:BackgroundThe growing tendency among opioid addicts to misuse multiple other drugs should lead clinicians and researchers to search for new pharmacological strategies in order to prevent life-threatening complications and minimize withdrawal symptoms during polydrug detoxification.MethodsA non-randomised, open-label in-patient detoxification study was used to compare the short-time efficacy of a standardised regimen comprising 6 days Buprenorphine and 10 days Valproate (BPN/VPA) (n = 12) to a control group (n = 50) who took a 10-day traditional Clonidine/Carbamazepine (CLN/CBZ) regimen. Sixty-two dependent subjects admitted to a detoxification unit were included, all dependent on at least opioids and benzodiazepines. Other dependencies were not excluded.ResultsIn the BPN/VPA group, 8 out of 12 patients (67%) completed treatment compared with 25 of 50 patients (50%) in the CLN/CBZ group; this difference between the groups was non-significant (p = 0.15). Withdrawal symptoms were reduced in both groups, but only the BPN/VPA group achieved a reduction in withdrawal symptoms from day one. The difference between the two groups was significantly in favour of the BPN/VPA group for days 2 (p < 0.001), 3 (p < 0.05), 4 (p < 0.001), 5 (p < 0.01), 7 (p < 0.01) and 8 (p < 0.05). The BPN/VPA combination did not affect blood pressure, pulse or liver function, and the total burden of side-effects was experienced as modest. There appeared to be no pharmacological interactions of clinical concern, based on measurement of Buprenorphine and Valproate serum levels. Both the patients and the staff were satisfied with the standardised treatment combination.ConclusionOverall, the combination of Buprenorphine and Valproate seems to be a safe and promising method for treating multiple drug withdrawal symptoms. The results of this study suggest that the BPN/VPA combination is potentially a better detoxification treatment for polydrug withdrawal than the traditional treatment with Clonidine and Carbamazepine. However, a randomised, double-blind study with a larger sample size to confirm our results is recommended.

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Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal.

Publications

Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal.

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