Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens

Stinus, L.; Nadaud, D.; Jauregui, J; Kelley, Ann E.

doi:10.1016/0006-3223(86)90006-5

Cited by 44 publications

(13 citation statements)

References 48 publications

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“…While we did not compare core with shell subregions in this study, the ability of the MOR antagonist CTAP to block cocaine-primed cocaine seeking suggests that β-endorphin is released in the vicinity of the medial NAc. Given that the locomotor activating effects of intra-NAc MOR- and DOR-selective agonists are not attenuated by dopamine depletion or chronic dopamine receptor blockade (Stinus et al , 1986; Churchill and Kalivas, 1992), it is likely that cocaine seeking elicited by MOR and DOR stimulation is mediated independent of dopamine release in the NAc. Furthermore, dopamine depletion leads to supersensitivity to MOR but not DOR agonist infusions in locomotor tests (Churchill and Kalivas, 1992).…”

Section: Discussionmentioning

confidence: 99%

Role of Mu- and Delta-Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior

Simmons

Self

2009

Neuropsychopharmacol

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Previous studies suggest that opioid receptors in the ventral tegmental area (VTA), but not the nucleus accumbens (NAc), play a role in relapse to drug-seeking behavior. However, environmental stimuli that elicit relapse also release the endogenous opioid β-endorphin in the NAc. Using a within–session extinction/reinstatement paradigm in rats that self-administer cocaine, we found that NAc infusions of the mu opioid receptor (MOR) agonist DAMGO moderately reinstated responding on the cocaine-paired lever at low doses (1.0–3.0 ng/side), whereas the delta opioid receptor (DOR) agonist DPDPE induced greater responding at higher doses (300–3000 ng/side) that also enhanced inactive lever responding. Using doses of either agonist that induced responding on only the cocaine-paired lever, we found that DAMGO-induced responding was blocked selectively by pretreatment with the MOR antagonist CTAP, while DPDPE-induced responding was selectively blocked by the DOR antagonist naltrindole. Cocaine-primed reinstatement was blocked by intra-NAc CTAP but not naltrindole, indicating a role for endogenous MOR-acting peptides in cocaine-induced reinstatement of cocaine-seeking behavior. In this regard, intra-NAc infusions of β-endorphin (100–1000 ng/side) induced marked cocaine-seeking behavior, an effect blocked by intra-NAc pretreatment with the MOR but not DOR antagonist. Conversely, cocaine seeking elicited by the enkephalinase inhibitor thiorphan (1–10 μg/side) was blocked by naltrindole but not CTAP. MOR stimulation in more dorsal caudate-putamen sites was ineffective, while DPDPE infusions induced cocaine seeking. Together, these findings establish distinct roles for MOR and DOR in cocaine relapse, and suggest that NAc MOR could be an important therapeutic target to neutralize the effects of endogenous β-endorphin release on cocaine relapse.

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Section: Discussionmentioning

confidence: 99%

Role of Mu- and Delta-Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior

Simmons

Self

2009

Neuropsychopharmacol

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“…It seems clear that opiates have reinforcing actions in nucleus accumbens (Olds, 198%;Goeders et al, 1984;Zito et al, 1985) as well as in the ventral tegmental area, and chronic neuroleptic treatment and dopaminedepleting lesions can increase the effectiveness of opiates as reinforcers and as psychomotor stimulants (Stinus et al, 1985(Stinus et al, , 1986(Stinus et al, , 1989. Thus it is possible that while the ventral tegmental actions of heroin are important for heroin self-administration in intact animals, nucleus accumbens mechanisms come strongly into play in dopamine-challenged animals.…”

Section: Discussionmentioning

confidence: 99%

Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self‐administration

Wise

Leone

Rivest

et al. 1995

Synapse

172

110

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Extracellular dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high-performance liquid chromatography during intravenous heroin self-administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150-300% when unit dosages of 0.05-0.2 mg/kg were given. Increasing the work requirement from FR-1 to FR-10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever-pressing rates increased 20-fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self-administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin "craving" can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal.

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“…Injections of the opioid antagonist methylnaloxonium into the NAcc, for example, have been shown to block locomotion induced by systemic heroin in rats (Amalric and Koob, 1985). However, while DA is not necessary for opioid-induced locomotion in rats, chronic blockade of dopaminergic transmission by either mesolimbic 6-OHDA lesions (Stinus et al, 1985) or prolonged systemic neuroleptic drugs (Stinus et al, 1986) results in supersensitivity to locomotion induced by NAcc injections of morphine, suggesting that a functional DA system in fact reduces sensitivity to NAcc opioid-induced locomotion.…”

Section: Rewarding Effects Of Opioids and Dopaminementioning

confidence: 99%

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

Steidl

Wasserman

Blaha

et al. 2017

Neuroscience & Biobehavioral Reviews

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Opioids, such as morphine or heroin, increase forebrain dopamine (DA) release and locomotion, and support the acquisition of conditioned place preference (CPP) or self-administration. The most sensitive sites for these opioid effects in rodents are in the ventral tegmental area (VTA) and rostromedial tegmental nucleus (RMTg). Opioid inhibition of GABA neurons in these sites is hypothesized to lead to arousing and rewarding effects through disinhibition of VTA DA neurons. We review findings that the laterodorsal tegmental (LDTg) and pedunculopontine tegmental (PPTg) nuclei, which each contain cholinergic, GABAergic, and glutamatergic cells, are important for these effects. LDTg and/or PPTg cholinergic inputs to VTA mediate opioid-induced locomotion and DA activation via VTA M5 muscarinic receptors. LDTg and/or PPTg cholinergic inputs to RMTg also modulate opioid-induced locomotion. Lesions or inhibition of LDTg or PPTg neurons reduce morphine-induced increases in forebrain DA release, acquisition of morphine CPP or self-administration. We propose a circuit model that links VTA and RMTg GABA with LDTg and PPTg neurons critical for DA-dependent opioid effects in drug-naïve rodents.

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Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens

Cited by 44 publications

References 48 publications

Role of Mu- and Delta-Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior

Role of Mu- and Delta-Opioid Receptors in the Nucleus Accumbens in Cocaine-Seeking Behavior

Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self‐administration

Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons

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