Rivastigmine reduces “likely to use methamphetamine” in methamphetamine-dependent volunteers

Garza, Richard De La; Newton, Thomas F.; Haile, Colin N.; Yoon, Jin Ho; Nerumalla, Chandra S.; Mahoney, James J.; Aziziyeh, A.

doi:10.1016/j.pnpbp.2011.12.014

Cited by 28 publications

(25 citation statements)

References 29 publications

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“…methamphetamine was not affected by rivastigmine and only 2 of 10 self-reported subjective effects [i.e., 'anxiousness' and 'desire (for amphetamine)'] were significantly decreased by rivastigmine [27]. A more recent report using higher doses [28] also indicates that rivastigmine reduces methamphetamine-induced subjective effects, but not self-administration in the human behavioral laboratory. These somewhat disappointing results mirror those of Grasing et al's [29] own human laboratory data obtained with donepezil: the positive subjective effects of i.v.…”

mentioning

confidence: 85%

Acetylcholine, Drug Reward and Substance Use Disorder Treatment: Intra- and Interindividual Striatal and Accumbal Neuron Ensemble Heterogeneity May Explain Apparent Discrepant Findings

Prast¹,

Kummer²,

Barwitz³

et al. 2012

Pharmacology

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Converging evidence from different independent laboratories suggests that acetylcholine may play an important role in drug reward and that modulation of the cholinergic system may be useful for the treatment of substance use disorders. In this commentary, we try to reconcile apparently discrepant animal behavioral, human behavioral and clinical data with a unifying hypothesis positing that the modulation of drug-versus natural stimuli-mediated reward by cholinergic interneurons in the nucleus accumbens (and the dorsal striatum) is restricted to distinct neuron ensembles that show considerable intra- and interindividual variation with respect to their spatial distribution. The precise targeting of these interindividually variable neuron ensembles would be a prerequisite for a successful pharmacotherapy based on the modulation of the cholinergic system. We also provide experimental data to support our unifying hypothesis.

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mentioning

confidence: 85%

Acetylcholine, Drug Reward and Substance Use Disorder Treatment: Intra- and Interindividual Striatal and Accumbal Neuron Ensemble Heterogeneity May Explain Apparent Discrepant Findings

Prast¹,

Kummer²,

Barwitz³

et al. 2012

Pharmacology

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“…Pharmacotherapies that correct dopaminergic hypofunction during meth abstinence have been identified as possible meth-cessation medications (De La Garza et al, 2012; Longo et al, 2010; Reichel et al, 2009; Verrico et al, 2013). Nicotinic acetylcholine receptors (nAChRs) can modulate dopamine release (Dobbs & Mark, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Nicotinic acetylcholine receptors (nAChRs) can modulate dopamine release (Dobbs & Mark, 2012). In fact, medications that effectively increase acetylcholine by inhibiting acetylcholinesterase reduce the positive subjective effects of meth (De La Garza et al, 2008a; De La Garza 2008b; De La Garza et al, 2012). Additionally, varenicline (Chantix ® ), a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, (Coe et al, 2005a; Mihalak et al, 2006) can reduce the positive subjective effects of meth in humans, an effect that may reflect nAChR agonism reversing dopaminergic hypofunction (Verrico et al, 2014; Zorick et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in male rats

Pittenger

Barrett

Chou

et al. 2017

Behavioural Brain Research

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Methamphetamine (meth) addiction is a costly burden to both the individual user and society as a whole. Establishing effective pharmacotherapies to treat meth dependence is needed to help solve this health problem. The study reported herein examined the effects of varenicline, a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, on meth self-administration and reinstatement in male Sprague-Dawley rats. Following indwelling jugular catheter surgery, rats were either trained to self-administer meth or saline on a variable ratio (VR) 3 schedule of reinforcement. Self-administration sessions (2 hour duration; 19 total sessions) were conducted daily. The effect of varenicline pretreatment on meth and saline self-administration was then determined using a within-study design. All rats received varenicline (0.0, 0.3, 1.0, and 3.0 mg/kg) prior to 4 different test sessions. Dose order was randomly assigned and each test was separated by 2 standard self-administration sessions to assess stability of responding. Fifteen extinction sessions (no meth available) followed the last test. Extinction was followed by meth-primed (0.3 mg/kg IP) reinstatement tests to examine the effect of varenicline on meth-seeking behavior. All rats again received all doses of varenicline over 4 separate reinstatement tests performed on 4 consecutive days. Varenicline did not alter self-administration of meth or saline. Additionally, the 0.3 and 1.0 doses of varenicline non-specifically increased active lever responding during the reinstatement test sessions. This latter finding suggests that varenicline may increase relapse liability and should not be utilized as pharmacotherapy to treat meth dependence.

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“…Dopaminergic hypofunction during drug abstinence likely contributes to meth dependence (Volkow et al , 2001b). Some medications (e.g., bupropion, modafinil, dextroamphetamine, rivastigmine) that assist in recovery of dopaminergic function following meth abuse are potential therapeutics for meth cessation (De La Garza et al , 2012; De La Garza et al , 2010; Elkashef et al , 2008; Heinzerling et al , 2014; Longo et al , 2010; McGregor et al , 2008; Newton et al , 2005, 2006; Rau et al , 2005; Reichel et al , 2008; Reichel et al , 2009; Verrico et al , 2013; Volkow et al , 2009). Activation of nicotinic acetylcholine receptors (nAChRs) increases dopamine release (Dobbs and Mark, 2012).…”

Section: Introductionmentioning

confidence: 99%

The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats

Pittenger

Barrett

Chou

et al. 2016

Behavioural Brain Research

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While research has revealed heightened vulnerability to meth addiction in women, preclinical models rarely use female subjects when investigating meth seeking and relapse. The goal of the present study was to examine the effects of varenicline (Chantix®), a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, on meth self-administration and reinstatement in female rats. Sprague-Dawley rats were surgically implanted with an indwelling jugular catheter. Half of the rats were then trained to self-administer meth (0.056 mg/kg/infusion) on a variable ratio 3 schedule of reinforcement; the other half earned intravenous saline during daily, 2 hour sessions. When responding stabilized, varenicline (0.0, 0.3, 1.0, 3.0 mg/kg) was tested to determine how it altered meth taking. Varenicline was probed on 4 test days; each test separated by 2 standard self-administration sessions to assure responding remained stable. Following this testing was 15 extinction sessions. Twenty-four hours after the last extinction session were four consecutive days of meth-primed reinstatement. The same 4 doses of varenicline were examined to determine how it altered reinstatement triggered by 0.3 mg/kg meth (IP). Rats readily self-administered meth. The higher doses of varenicline did not affect meth-taking in a specific fashion as active lever pressing wasalso slightly reduced in rats that has access to saline in the self-administration phase. Female rats displayed robust meth-primed reinstatement. Notably, the lower doses of varenicline increased meth-primed reinstatement. This amplified susceptibility to reinstatement (i.e., relapse) may be an impediment for the use of varenicline as a therapeutic to treat meth use disorder.

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Rivastigmine reduces “likely to use methamphetamine” in methamphetamine-dependent volunteers

Cited by 28 publications

References 29 publications

Acetylcholine, Drug Reward and Substance Use Disorder Treatment: Intra- and Interindividual Striatal and Accumbal Neuron Ensemble Heterogeneity May Explain Apparent Discrepant Findings

Acetylcholine, Drug Reward and Substance Use Disorder Treatment: Intra- and Interindividual Striatal and Accumbal Neuron Ensemble Heterogeneity May Explain Apparent Discrepant Findings

The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in male rats

The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats

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