Association between depressive behavior and absence of serotonin-dopamine interaction in the nucleus accumbens

Zangen, Abraham; Nakash, R.; Overstreet, David H.; Yadid, Gal

doi:10.1007/s002130100746

Cited by 155 publications

(101 citation statements)

References 17 publications

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“…Fluoxetine administration directly enhances 5-HT activity, which has been shown to facilitate dopamine release in the nucleus accumbens (Benloucif and Galloway 1991;De Deuwaerdere et al 1996), and increase sensitivity to reward (Sasaki-Adams and Kelley 2001). Conversely, decreased 5-HT release inhibits DA activity (Ichikawa et al 1995), a mechanism that has been linked with acquisition of anhedonia (Harrison et al 2001;Zagen et al 2001). Plausibly, therefore, reduction in positive affect during nicotine deprivation may be engendered by decreased 5-HT activity with consequent inhibition of DA release.…”

Section: Discussionmentioning

confidence: 99%

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial

et al. 2004

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Rationale-Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder. Little is known about fluoxetine's influence on mood changes after quitting smoking, which often resemble sub-clinical depression.Objectives-The present study, a re-analysis of previously published data , examined fluoxetine's effect on changes in negative and positive affect following quitting smoking.Methods-Adult smokers (n=175) without clinically significant depression were randomized on a double-blind basis to receive fluoxetine hydrochloride (30 or 60 mg daily) or placebo for 10 weeks in combination with cognitive-behavioral therapy (CBT) for smoking cessation. We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect.Results-Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence, plasma fluoxetine metabolites, and change in cotinine (a nicotine metabolite) at each visit. Relative to placebo, those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [t(526) Conclusions-Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation.

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Section: Discussionmentioning

confidence: 99%

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial

et al. 2004

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“…Although neurobiological theories of depression have focused on 5-HT and/or NE systems per se, recent evidence suggests a contributing role for DA in symptoms and/or efficacy of therapeutics (Zangen et al, 2001). Several antidepressant drugs (e.g.…”

Section: Depression/anxietymentioning

confidence: 99%

“…These data have important implications not only for the management and prevention of drug abuse, but also for the treatment of reduced motivation and response to reward, such as the anhedonia that is characteristic of withdrawal from drugs of abuse as well as disorders such as schizophrenia and depression. In fact, studies suggest that antidepressant efficacy at treating lack of motivation and anhedonia may involve increased DA release in the NA (Zangen et al, 2001). …”

Section: Summary and Implicationsmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

525

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…FST creates a situation of despair, and allows evaluation of the ability of the animal to adopt active strategies in inescapable stressful situation; failure to do so is indicative of a depression-like state [21,25] . We employed a modified FST, when the animals underwent a single five-minute trial [26]; such a modification of the classic Porsolt test [22] was shown to be relevant for both examining depressive state, and for screening antidepressant agents. Furthermore, since the first swim trial under conditions of classic Porsolt test plays a role of depressogenic treatment [22], such a procedure might complicate the interpretation of behavioral data in the already depressed animals.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…One of core symptoms of depression is the loss of the ability to experience pleasure, referred to as anhedonia [21,26,27]. In rats, anhedonia can be assessed by the loss of taste preference; while normal animals prefer sweetened water over regular water, animals with depression do not exhibit such a preference [23,24,[28][29][30].…”

Section: Behavioral Testsmentioning

confidence: 99%

Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Mazarati¹,

Shin²,

Auvin³

et al. 2007

Epilepsy & Behavior

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Depression is a frequent comorbidity in epilepsy patients. A variety of biological factors may underlie epilepsy-associated depression. We examined whether kindling-induced chronic increase in seizure susceptibility is accompanied by behavioral symptoms of depression. Three week-old Wistar rats underwent rapid kindling -84 initially subconvulsant electrical stimulations of ventral hippocampus delivered every five minutes -followed by depression-specific behavioral tests performed two and four weeks later. Kindled animals exhibited sustained increase in the immobility time in the forced swim test and the loss of taste preference towards calorie-free saccharin, as compared to controls. Initial loss of preference towards the intake of calorie-containing sucrose was followed by the increased consumption at four weeks. At both time points, animals exhibited enhanced seizure susceptibility upon test stimulations of the hippocampus. We conclude that neuronal plastic changes associated with kindling state are accompanied by the development of depressive behavior.

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Association between depressive behavior and absence of serotonin-dopamine interaction in the nucleus accumbens

Abstract: The inability of serotonin to stimulate dopamine release in the nucleus accumbens, thereby leading to anhedonia and lack of motivation, may therefore be an essential factor in the onset of depression and a target for modulation by antidepressant drugs.

Cited by 155 publications

References 17 publications

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Kindling epileptogenesis in immature rats leads to persistent depressive behavior

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