Chronic morphine induces long-lasting changes in acetylcholine release in rat nucleus accumbens core and shell: an in vivo microdialysis study

Fiserová, M; Consolo, S.; Kršiak, M

doi:10.1007/s002130050866

Cited by 49 publications

(21 citation statements)

References 45 publications

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“…Acutely, morphine reduces acetylcholine release in the NAc core and shell, and a morphine priming injection (at a dose that had no effect acutely), reduces NAc acetylcholine after 5 days withdrawal from repeated morphine exposure. However, after 15 and 35 days of withdrawal a morphine priming injection increases acetylcholine release in the NAc over chronic saline treated rats (Fiserova et al, 1999). Therefore, opiates may dynamically regulate cholinergic transmission, possibly correlating with presence or absence of withdrawal symptoms.…”

Section: Acetylcholinementioning

confidence: 97%

Microdialysis and the neurochemistry of addiction

Torregrossa

Kalivas

2008

Pharmacology Biochemistry and Behavior

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Drug addiction is a process beginning with the initial exposure to a drug of abuse, and leading, in some individuals, to chronic habitual use, and high rates of relapse. Microdialysis allows researchers to monitor the neurochemical changes that occur in the brain after the initial exposure to a drug, and the neurochemical changes that occur with repeated exposure. These changes in the brain are often referred to as drug-induced neuroplasticity, and the aim of this article is to review studies that have utilized microdialysis to increase our understanding of the neuroplasticity that occurs in the process of addiction. We will review how several neurotransmitter systems, including glutamate, GABA, the monoamines, and others, are altered after chronic drug exposure, and how microdialysis can be used to determine if putative treatments for addiction can reverse the drug-induced neuroplasticity in these systems. We will also briefly discuss our recent research using a known change in GABA neurotransmission that occurs during reinstatement of drug-seeking to screen for possible novel treatments to prevent relapse. Overall, microdialysis in combination with other behavioral and pharmacological techniques has greatly increased our understanding of addiction related neuroplasticity, and provides a means for discovering new ways to prevent these changes and treat addiction.

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Section: Acetylcholinementioning

confidence: 97%

Microdialysis and the neurochemistry of addiction

Torregrossa

Kalivas

2008

Pharmacology Biochemistry and Behavior

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“…Mice that received mecamylamine and mice null for the b2 nicotinic subunit displayed decreased place preference for cocaine compared with wild-type (WT) littermates (Zachariou et al, 2001). Interestingly, psychostimulants enhance release of acetylcholine (Ach) in the nucleus accumbens (NAc) and increase responsiveness of cholinergic neurons during acute and repeated drug exposure (Fiserová et al, 1999;Nestby et al, 1997). In humans, Budney et al (1993) reported comorbidity of cigarette smoking in cocaine addicts.…”

Section: Introductionmentioning

confidence: 99%

Differential Roles of α6β2* and α4β2* Neuronal Nicotinic Receptors in Nicotine- and Cocaine-Conditioned Reward in Mice

Sanjakdar

Maldoon

Marks

et al. 2014

Neuropsychopharmacol

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Mesolimbic a6* nicotinic acetylcholine receptors (nAChRs) are thought to have an important role in nicotine behavioral effects. However, little is known about the role of the various a6*-nAChRs subtypes in the rewarding effects of nicotine. In this report, we investigated and compared the role of a6*-nAChRs subtypes and their neuro-anatomical locus in nicotine and cocaine reward-like effects in the conditioned place preference (CPP) paradigm, using pharmacological antagonism of a6b2* nAChRs and genetic deletion of the a6 or a4 subunits in mice. We found that a6 KO mice exhibited a rightward shift in the nicotine dose-response curve compared with WT littermates but that a4 KO failed to show nicotine preference, suggesting that a6a4b2*-nAChRs are involved. Furthermore, a6b2* nAChRs in nucleus accumbens were found to have an important role in nicotine-conditioned reward as the intra-accumbal injection of the selective a6b2* a-conotoxin MII [H9A; L15A], blocked nicotine CPP. In contrast to nicotine, a6 KO failed to condition to cocaine, but cocaine CPP in the a4 KO was preserved. Intriguingly, a-conotoxin MII [H9A; L15A], blocked cocaine conditioning in a4 KO mice, implicating a6b2* nAChRs in cocaine reward. Importantly, these effects did not generalize as a6 KO showed both a conditioned place aversion to lithium chloride as well as CPP to palatable food. Finally, dopamine uptake was not different between the a6 KO or WT mice. These data illustrate that the subjective rewarding effects of both nicotine and cocaine may be mediated by mesolimbic a6b2* nAChRs and that antagonists of these receptor subtypes may exhibit therapeutic potential.

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“…Although stereotypy is typically elicited by high doses of morphine in rats [16,17], some investigators suggest that a low dose of morphine (2 and 4 mg/kg) also generates marked stereotyped behaviors [14,18]. Therefore, in addition to quantifying locomotor activity, the stereotyped behaviors of the animals were also rated.…”

Section: Methodsmentioning

confidence: 99%

The expression of morphine-induced behavioral sensitization depends more on treatment regimen and environmental novelty than on conditioned drug effects

Liang

Peng

et al. 2010

Chin. Sci. Bull.

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Both conditioned responses (CRs) and sensitized behaviors induced by addictive drugs are considered to reflect drug-seeking motivation. Based on an excitatory conditioning model of behavioral sensitization, this work hypothesizes that conditioned locomotor activity and locomotor sensitization concomitantly occur using different drug treatment regimens. In the present study, conditioned locomotor activity and sensitized locomotion and stereotypy are assessed with pretreatment of two doses of morphine in a familiar or novel environment. When rats are trained with morphine (3 or 5 mg/kg) in an environment to which the animals are habituated, a CR but not contextual sensitization is induced when tested after 1 week of abstinence. When rats receive the 5 mg/kg dose of morphine immediately after placement into a novel environment, the same results are obtained, but when the drug dose is decreased to 3 mg/kg, both the CR and contextual sensitization are observed. Therefore, the sensitized behaviors, rather than the CR produced by morphine pretreatment, appear to be dependent on the drug treatment regimen and environmental novelty, suggesting that different mechanisms may be involved in the expression of the CR and contextual sensitization. morphine, conditioning, sensitization, locomotion, stereotypy Citation: Liang J, Peng Y H, Ge X X, et al. The expression of morphine-induced behavioral sensitization de-pends more on treatment regimen and environmental novelty than on conditioned drug effects.Repeated intermittent exposure to potentially addictive drugs leads to pathological levels of incentive salience attributed to drugs and drug-associated cues [1,2]. According to the excitatory conditioning model, sensitization is context-specific because it occurs in response to Pavlovian conditioning [3,4]. However, dissociation between the conditioned response (CR) and behavioral sensitization has been found in many studies, e.g. amphetamine and methylenedioxymethamphetamine (MDMA) induced conditioned hyperlocomotion in the absence of prior sensitization [5,6]. By contrast, extinction of the post-sensitization CR did not impede the subsequent expression of contextual sensitization [7,8]. The behavioral effects induced by frequently *Corresponding author (email: zhengxg@psych.ac.cn) abused drugs are significantly impacted by the drug dose and the experimental drug administration design [9−12]. The present study sought to verify the relationship between CR and drug-induced sensitized behaviors using different morphine-treatment regimens by altering the drug doses and the environment novelty.In the present study, when rats were trained with morphine (5 mg/kg) in an environment to which the animals were habituated, a CR occurred, but not contextually sensitized behaviors, when tested after a 1-week abstinence period. The results were similar when the dose of morphine was reduced to a 3 mg/kg pretreatment. This diminished sensitization of locomotor activity did not derive from any "masking effect" of the emergence of stereotyped beh...

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Chronic morphine induces long-lasting changes in acetylcholine release in rat nucleus accumbens core and shell: an in vivo microdialysis study

Cited by 49 publications

References 45 publications

Microdialysis and the neurochemistry of addiction

Microdialysis and the neurochemistry of addiction

Differential Roles of α6β2* and α4β2* Neuronal Nicotinic Receptors in Nicotine- and Cocaine-Conditioned Reward in Mice

The expression of morphine-induced behavioral sensitization depends more on treatment regimen and environmental novelty than on conditioned drug effects

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