Diminished conditioned responding to the nicotine stimulus by antidepressant drugs with differing specificity for the serotonin and norepinephrine transporter

Dion, Amanda M.; Sanderson, Scott C.; Murrin, L. Charles; Bevins, Rick A.

doi:10.1016/j.pbb.2011.10.003

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…The 0.05 mg/kg dose was selected for that experiment because it prompted partial substitution for the nicotine CS in a wide range of studies. Further, this dose is on the lower end of the range of median effective doses (ED 50 ) reported when the 0.4 mg/kg nicotine served as the CS (range = 0.033-0.099 mg/kg; mean = 0.072 mg/kg; see Murray et al, 2007aMurray et al, , 2007bStruthers et al, 2009;Murray et al, 2010;Reichel et al, 2010;Wilkinson et al, 2010;Dion et al, 2012). The 0.05 mg/kg dose of nicotine evoked a partial goal-tracking CR in the first five of the six 20-min extinction sessions.…”

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confidence: 99%

Interoceptive conditioning with the nicotine stimulus

Polewan

Savala

Bevins

2013

Behavioural Pharmacology

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Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

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confidence: 99%

Interoceptive conditioning with the nicotine stimulus

Polewan

Savala

Bevins

2013

Behavioural Pharmacology

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“…Ligands that act, in part, by inhibiting monoamine transporters interfere with nicotine-evoked goal-tracking and nicotine self-administration (Di Chiara, 2000; Dion et al , 2012; Rauhut et al , 2003; Wilkinson et al , 2010). Thus, the impact of iptakalim per se on dopamine and serotonin transporter function was evaluated.…”

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confidence: 99%

“…For example, bupropion, a dopamine transporter inhibitor, fully substitutes for the stimulus effects of nicotine. Conversely, the SERT inhibitor, citalopram, blocks the conditioned response controlled by the nicotine stimulus (Dion et al , 2012). However, since iptakalim did not appreciably inhibit SERT or DAT function, another mechanism(s) likely underlies its effects on the stimulus and reinforcing effects of nicotine.…”

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confidence: 99%

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Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine

et al. 2013

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Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a response-independent manner only on nicotine sessions. On intervening test days, rats were pretreated with iptakalim (10, 30, 60 mg/kg, IP). Results revealed that iptakalim attenuated nicotine-evoked responding controlled by the nicotine stimulus in a dose-dependent manner. In a separate study, the impact of iptakalim on the reinforcing effects of nicotine was investigated by training rats to lever-press to self-administer nicotine (0.03 mg/kg/infusion). Results revealed that pretreatment with iptakalim (1, 3, 6 mg/kg, IV) decreased nicotine intake (i.e., less active lever responding). Neither behavioral effect was due to a non-specific motor effect of iptakalim, nor to an ability of iptakalim to inhibit DA transporter (DAT) or serotonin transporter (SERT) function. Together, these finding support the notion that iptakalim may be an effective pharmacotherapy for increasing smoking cessation and better understanding its action could contribute medication development.

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“…Despite having apparent limited success in very early clinical studies [ 91 ], recent preclinical studies indicate that it may be more efficacious with regards to the modulating the affective aspects of nicotine intake. A study in rodents identified a decrease in conditioned responding to the nicotine CS and thus reducing incentive value of drug administered [ 92 ]. An analogue of imipramine, has also shown recent success preclinically [ 93 ].…”

Section: Tricyclic Antidepressantsmentioning

confidence: 99%

Why are Antidepressant Drugs Effective Smoking Cessation Aids?

Shoaib

Buhidma

2018

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BackgroundBefore the advent of varenicline, antidepressant drugs were reported to exhibit better clinical efficacy than nicotine replacement therapy as smoking cessation aids. The most studied is bupropion, a clinically-effective antidepressant, the first to be marketed throughout Europe for smoking cessation. Since depression and tobacco smoking have a high incidence of co-occurrence, this would implicate an underlying link between these two conditions. If this correlation can be confirmed, then by treating one condition the related state would also be treated.ObjectivesThis review article will evaluate the various theories relating to the use of antidepressant drugs as smoking cessation aids and the underlying mechanisms link tobacco smoking and depression to explain the action of antidepressants in smoking cessation. One plausible theory of self-medication which proposes that people take nicotine to treat their own depressive symptoms and the affective withdrawal symptoms seen with abstinence from the drug. If the depression can instead be treated with antidepressants, then they may stop smoking altogether. Another theory is that the neurobiological pathways underlying smoking and depression may be similar. By targeting the pathways of depression in the brain, antidepressants would also treat the pathways affected by smoking and ease nicotine cravings and withdrawal. The role of genetic variation predisposing an individual to depression and initiation of tobacco smoking has also been discussed as a potential link between the two conditions. Such variation could either occur within the neurobiological pathways involved in both disorders or it could lead to an individual being depressed and self-medicating with nicotine.

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Diminished conditioned responding to the nicotine stimulus by antidepressant drugs with differing specificity for the serotonin and norepinephrine transporter

Cited by 6 publications

References 36 publications

Interoceptive conditioning with the nicotine stimulus

Interoceptive conditioning with the nicotine stimulus

Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine

Why are Antidepressant Drugs Effective Smoking Cessation Aids?

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