High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation

Caldarone, Barbara J.; Harrist, Alexia; Cleary, Muriel A.; Beech, Robert D.; King, Sarah L.; Picciotto, Marina R.

doi:10.1016/j.biopsych.2004.08.010

Cited by 117 publications

(130 citation statements)

References 40 publications

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“…This, along with the observation that β2-nAchR knockout mice are more prone to learned helplessness [13], emphasizes that there is a strong relationship between nicotinic receptor modulation and mood control. Nicotine, administered acutely and chronically, shows an antidepressant-like effect on the behavior of FSL rats (bred for cholinergic hypersensitivity) in the forced swim test [79], implicating the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats.…”

Section: Discussionmentioning

confidence: 95%

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

Kroes¹,

Burgdorf²,

Otto³

et al. 2007

Behavioural Brain Research

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Gene expression profiles in the periaqueductal gray (PAG) of adult Long-Evans rats as a function of a stressful social defeat in inter-male fighting encounters were examined. This social subordination model mimics prototypical behavioral changes that parallel aspects of clinical depression, has been postulated to simulate early changes in the onset of depression in the losers, and has been successfully utilized for the evaluation of antidepressant activity. 22-kHz ultrasonic vocalizations (USVs) have been shown to reflect negative emotional states akin to anxiety and depression. Social defeat is the most robust and reliable method of eliciting these calls. The PAG has been shown to be a key brain region for the generation of 22-kHz ultrasonic vocalizations, and 22-kHz USVs have been shown to be controlled by the mesolimbic cholinergic system. In this present study we examined gene expression changes in the PAG of social subordinate rats compared to dominant rats (that do not exhibit 22-kHz USVs). We found that social defeat significantly altered the genes associated with cholinergic synaptic transmission in the PAG. The most robust of these were the increased expression of the β2 subunit of the nicotinic acetylcholine receptor (CHRNB2) and the T-subunit of acetylcholinesterase (ACHE) in the subordinate animals. These changes were corroborated by qRT-PCR and found to be exclusive to the PAG compared to seven other brain regions examined. These data suggest that cholinergic transmission in the PAG is involved in the generation of 22-kHz USVs and provide potential therapeutic targets for the treatment of affective disorders.

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Section: Discussionmentioning

confidence: 95%

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

Kroes¹,

Burgdorf²,

Otto³

et al. 2007

Behavioural Brain Research

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“…19 A relationships has also been found between smoke and depression, 20 and both agonists (such as nicotine) and antagonists are effective in animal models of depression. 21,22 Several nicotinic agonists are under development as analgesics, 23 and ABT-089, a compound in phase II for AD, is also under evaluation for Attention-Deficit Hyperactivity Disorder (ADHD) in adults. 24 Varenicline, an orally active α4β2 nicotinic partial agonist, is now in clinical trials for smoking cessation.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and binding affinity of new nicotinic ligands

Guandalini¹,

Martini²,

Gratteri³

et al. 2006

Arkivoc

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Nicotinic ligands can be potentially useful as drugs for the management of several important pathologies as well as pharmacological tools to characterize nicotinic receptor subtypes. The design of new nicotinic ligands has been carried out by applying the 3D database search method; thus, the Cambridge Structural Database has been scanned with a query consisting in a pharmacophore substructure with 3D constraints. The nicotinic pharmacophoric features have been obtained from the structure of pyrido[3,4-b]homotropane (PHT), which represents a rigid template. The results of the query suggested the aminoalkylquinoline moiety as simple scaffold, and it was further refined using molecular modeling. Some of the synthesized compounds were found to interact with the central nicotinic receptor on rat cerebral cortex, showing affinity in the nanomolar range and displaying analgesic properties. The possible binding mode of these substances with a homology-built model of the nicotinic receptor has been analyzed by means of induced fit studies.

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“…Consistent with a role for nAChRs in regulation of anxiety-like behavior, mice lacking either the α4 subunit or the α7 subunit show less anxiety-like behaviors [122,142]. With respect to depression-like behavior, β2 KO mice do not respond to classical and atypical antidepressants, emphasizing the relationship between the cholinergic and the monoaminergic systems in mood disorders [143][144][145]. Interestingly, these mice are also less immobile in the forced swim and tail suspension tests at baseline, suggesting that β2* nAChRs may normally have a role in regulating mood.…”

Section: Genetically-manipulated Mouse Models: Beyond Addictionmentioning

confidence: 87%

Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction

Mineur

Picciotto

2008

Biochemical Pharmacology

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119

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Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotinerelated behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking.

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High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation

Cited by 117 publications

References 40 publications

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

Design, synthesis and binding affinity of new nicotinic ligands

Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction

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