Ability of baclofen to prevent somatic manifestations and neurochemical changes during nicotine withdrawal

Varani, Andrés Pablo; Moutinho, Lirane Machado; Calvo, Mariela; Balerio, Graciela N.

doi:10.1016/j.drugalcdep.2011.05.017

Cited by 18 publications

(50 citation statements)

References 41 publications

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“…In this sense, previous studies have shown that deficits in dopamine (DA) and 5-HT transmission in the striatum and cortex could play a role in mediating the somatic expression of NIC withdrawal syndrome (Fung et al, 1996;Slotkin and Seidler, 2007;Mannucci et al, 2007). Similarly, we recently found that striatal and cortical DA and 5-HT levels were decreased during NIC withdrawal (Varani et al, 2011). On the other hand, baclofen prevented the somatic manifestations and neurochemical changes induced by NIC withdrawal, suggesting a modulation of GABAergic inputs directly connected with 5-HTergic and DAergic neurons in the striatum and cortex (Varani et al, 2011).…”

Section: Discussionmentioning

confidence: 87%

“…In addition, the administration of baclofen, a GABA B receptor agonist, attenuates the antinociceptive, hypolocomotive (Aso et al, 2007) and rewarding effects induced by NIC (Le Foll et al, 2008). Also, we have previously found that baclofen prevents the neurochemical changes and behavioural manifestations of the mecamylamineinduced NIC withdrawal syndrome in mice (Varani et al, 2011). Furthermore, we have also shown that c-Fos expression was decreased in the caudate putamen and the dentate gyrus of hippocampus (Balerio et al, 2004) after mecamylamineprecipitated NIC withdrawal syndrome.…”

Section: Introductionmentioning

confidence: 74%

“…Similarly, we recently found that striatal and cortical DA and 5-HT levels were decreased during NIC withdrawal (Varani et al, 2011). On the other hand, baclofen prevented the somatic manifestations and neurochemical changes induced by NIC withdrawal, suggesting a modulation of GABAergic inputs directly connected with 5-HTergic and DAergic neurons in the striatum and cortex (Varani et al, 2011). Thereby, in the current study the lack of GABA B receptors would prevent the action of the released GABA, leading to a disinhibition of 5-HTergic and DAergic neurons.…”

Section: Discussionmentioning

confidence: 93%

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Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

et al. 2012

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 93%

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Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

et al. 2012

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“…Finally, acute administration of baclofen attenuated the somatic expression of withdrawal signs in animals made dependent on nicotine [153]. …”

Section: Baclofen and Sudsmentioning

confidence: 99%

Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review

Agabio¹,

Preti

Gessa

2013

Eur Addict Res

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Background: It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some psychoactive drugs. Aims and Methods: To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs. Results: Baclofen tolerability is generally considered to be good. Eleven RCTs investigated its effectiveness in the treatment of SUDs. Of these, 5 RCTs found that baclofen is effective, 5 RCTs found that it is ineffective and the results of 1 RCT were not appreciable because it did not achieve the preplanned level of participation. Conclusions: The number of RCTs on baclofen and SUDs is still low, and their results are divergent. Further RCTs should be undertaken, particularly with higher doses of baclofen. Its administration may be suggested in patients who fail to respond to other approved drugs or who are affected by liver disease that prevents their administration, or in patients affected by SUDs for which no approved drugs are available. Treatment should be conducted under strict medical supervision.

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“…In the case of antagonism with mecamylamine, which is used to induce nicotine withdrawal, animals may continue to consume nicotine in an attempt to overcome the aversive effects of nAChR antagonism. Conversely, baclofen blocks mecamylamine-induced withdrawal symptoms (Varani et al, 2011; 2014). Differences in mechanism of action and effects on withdrawal symptomology may explain the opposing effects of mecamylamine and R(+)-baclofen on oral nicotine consumption.…”

Section: Discussionmentioning

confidence: 99%

Developing a model of limited-access nicotine consumption in C57Bl/6J mice

Kasten

Frazee

Boehm

2016

Pharmacology Biochemistry and Behavior

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Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14 mg/ml nicotine in 0.2% saccharin reached over 6 mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated.

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Ability of baclofen to prevent somatic manifestations and neurochemical changes during nicotine withdrawal

Cited by 18 publications

References 41 publications

Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review

Developing a model of limited-access nicotine consumption in C57Bl/6J mice

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