Nicotinic–serotonergic interactions in brain and behaviour

Seth, Pallab; Cheeta, Survjit; Tucci, Sonia; File, Sandra E.

doi:10.1016/s0091-3057(01)00715-8

Cited by 140 publications

(96 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, these patterns may not be specific to nicotine effects on 5HT systems, since we found similar desensitization for cholinergic systems (Abreu-Villaça et al, 2004b;Seidler et al, 1992). Indeed, given the prominent role of cholinergic input in regulating 5HT synaptic activity (Cucchiaro and Commons, 2003;Rao et al, 2003;Seth et al, 2002), the parallel findings may reflect a primary effect of prenatal nicotine exposure on cholinergic synaptic activity and responsiveness, secondarily influencing 5HT systems (Abreu-Villaça et al, 2004b;Seidler et al, 1992;Slotkin, 1998Slotkin, , 2002Slotkin, , 2004. Superimposed on this overall effect, the cumulative neurotoxicity imposed by the combined prenatal and adolescent nicotine exposure may then account for the additional alterations in 5HT and AC responses that show directions of change opposite to those of either treatment alone (Abreu-Villaça et al, 2004a;Slotkin, 2002).…”

Section: Effects Of Prenatal Nicotine Exposure On the Response To Nicmentioning

confidence: 72%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT 1A and 5HT 2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

show abstract

Section: Effects Of Prenatal Nicotine Exposure On the Response To Nicmentioning

confidence: 72%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Because the effects of nicotine on receptor binding decay more rapidly in the adult [39], this relationship cannot be the direct result of the amount of nicotine self-administered, and indeed, there was no significant (p=0.45) relationship detected between striatal receptor binding and nicotine self-administration during weeks three and four, the period immediately preceding the binding determination. The striatum is an important site for nicotine-elicited reward function [32] and nicotine effects on striatal monoamine systems contribute to nicotine withdrawal symptoms [33], especially the craving that tends to subvert attempts at quitting smoking [43]. In keeping with this interpretation, striatal reward-associated pathways are desensitized to non-smoking related inputs in smokers, so that further nicotine intake becomes a required to sustain reward function [25].…”

Section: Discussionmentioning

confidence: 99%

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Levin

Lawrence

Petro

et al. 2007

Neurotoxicology and Teratology

133

105

View full text Add to dashboard Cite

Adolescence is the life stage when tobacco addiction typically begins. Adolescent neurobehavioral development may be altered by nicotine self-administration in a way that persistently potentiates addiction. Previously, we showed that female adolescent rats self-administer more nicotine than do adults and that the increased nicotine intake then persists through the transition to adulthood [23]. In the current study, male Sprague-Dawley rats were given access to nicotine via the standard operant IV self-administration procedure (nicotine bitartrate dose of 0.03 mg/kg/infusion). One group of male rats started during adolescence the other group started in young adulthood. After the end of the fourweek period of self-administration brain regions of the rats were assessed for α4β2 nicotinic receptor binding. We found that male rats, like females, show higher nicotine self-administration when starting during adolescence as compared to starting in adulthood (p<0.001). Indeed, the effect in adolescent males was even greater than that in females, with more than triple the rate of nicotine selfadministration vs. the adult-onset group during the first two weeks. The adolescent onset nicotineself-administering rats also had significantly greater high affinity nicotinic receptor binding in the midbrain and the striatum, whereas hippocampal binding did not differ between the age groups. Striatal values significantly correlated with nicotine self-administration during the first two weeks in the adult-onset group but not the adolescent-onset rats, suggesting that the differences in selfadministration may depend in part on underlying disparities in synaptic responses to nicotine. After the initial two weeks, nicotine self-administration in male rats declined toward adult-like levels, as the adolescent rats approached adulthood. This study showed that adolescent male rats selfadminister significantly more nicotine than do male adult rats, but that adolescent-onset nicotine selfadministration in male rats declines over weeks of continued use to approach adult-onset levels. In a previous study, we found that female rats also show greater nicotine self-administration with adolescent onset vs. adult onset, but that the females continued higher rates of self-administration into adulthood. Our results thus reinforce the concept that the adolescent brain is unusually receptive to the effects of nicotine in a manner that reinforces the potential for addiction.

show abstract

“…24 It is widely accepted that the acute systemic administration of nicotine enhances the release of 5HT in several brain regions of rats. [25][26][27] In contrast to the acute treatment, chronic nicotine administration decreases the concentration and biosynthesis of 5HT in the hippocampus or frontal cortex.…”

Section: Discussionmentioning

confidence: 99%

Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: Reversal by co‐administration of bupropion

Semba

Wakuta

2008

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Aim: Epidemiologic studies suggest the existence of a biological link between nicotine withdrawal and depression. To investigate the neuronal mechanisms of the precipitation of depression during smoking cessation, an animal model of nicotine withdrawal was used, and the expression of serotonin transporter (5HTT), abnormality of which is implicated in the pathogenesis of depression, was investigated. The effect of co-administration of bupropion, which has been clinically shown to ameliorate nicotine withdrawal symptoms, was also investigated in this model. Methods:Male Wistar rats were implanted with a minipump s.c., which delivered nicotine at a rate of 6 mg/kg per day for 12 days (days 1-12). Rats given chronic nicotine were killed on day 13, or 2 days after the removal of minipump (withdrawal day 2). In a separate experiment, bupropion (15 or 30 mg/kg per day) was injected into the nicotine infused rats on days 2-12. The expression of mRNA for 5HTT in the dorsal raphe was determined on in situ hybridization.Results: Chronic nicotine infusion resulted in the reduction of 5HTT mRNA expression, which lasted through withdrawal day 2. Co-administration of bupropion, however, significantly antagonized this reduction.Conclusions: Chronic nicotine infusion reduces the synthesis of 5HTT protein, which may consequently precipitate depression during nicotine withdrawal, but co-administration of bupropion may ameliorate withdrawal symptoms by counteracting nicotine's effect on 5HTT.

show abstract

Nicotinic–serotonergic interactions in brain and behaviour

Cited by 140 publications

References 110 publications

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: Reversal by co‐administration of bupropion

Contact Info

Product

Resources

About