Novel therapeutic approaches beyond the serotonin receptor

Duman, Ronald S.

doi:10.1016/s0006-3223(98)00031-6

Cited by 233 publications

(126 citation statements)

References 46 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…The mechanism of the antidepressant action of substance P receptor antagonists is unknown, but preclinical studies have shown that their interaction with monoamine systems is different than the interaction seen with the use of established antidepressant drugs (Kramer et a1 1998) Other novel strategies target antidepressant drugs "beyond" the receptors and include the modulation of post-receptor mechanisms, e.g. the intracellular messenger cyclic adenosine monophosphate (CAMP) pathways, including the brain-derived neurotrophic factor (BDNF) system (Duman et a1 1997;Duman 1998; Altar 1999).…”

Section: Re Vie W/m Ini-r E Vie W Bmentioning

confidence: 99%

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and Continuation Treatment of Major Depressive Disorder

Bauer

Whybrow²,

Angst

et al. 2002

The World Journal of Biological Psychiatry

337

150

View full text Add to dashboard Cite

Section: Re Vie W/m Ini-r E Vie W Bmentioning

confidence: 99%

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and Continuation Treatment of Major Depressive Disorder

Bauer

Whybrow²,

Angst

et al. 2002

The World Journal of Biological Psychiatry

337

150

View full text Add to dashboard Cite

“…Moreover, chronic administration of antidepressants can increase BDNF in the hippocampus and can prevent stress-induced decreases in hippocampal BDNF (Nibuya et al, 1995) and other damaging effects of stress on the hippocampus (see (Duman, 1998, Duman, 2004) for reviews). Both DG neurogenesis (Santarelli et al, 2003) and BDNF signaling (Saarelainen et al, 2003) are necessary for behavioral effects of antidepressants in animal models.…”

Section: Introductionmentioning

confidence: 99%

Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

et al. 2007

View full text Add to dashboard Cite

Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against stress-induced reductions of hippocampal BDNF protein.The observed prevention of stress-induced deceases in BDNF, however, occurred in a time course inconsistent with the prevention of learned helplessness by wheel running, which is evident following 6 weeks, but not 3 weeks, of wheel running. BDNF suppression in physically active rats was produced by administering a single injection of the selective serotonin reuptake inhibitor fluoxetine (10 mg/ kg) just prior to stress. Despite reduced levels of hippocampal BDNF mRNA following stress, physically active rats given the combination of fluoxetine and stress remained resistant against learned helplessness. Sedentary rats given both fluoxetine and stress still demonstrated typical learned helplessness behaviors. Fluoxetine by itself reduced BDNF mRNA in sedentary rats only, but did not affect freezing or escape learning 24 hours later. Finally, bilateral injections of BDNF (1 μg) into the dentate gyrus prior to stress prevented stress-induced reductions of hippocampal BDNF but did not prevent learned helplessness in sedentary rats.These data indicate that learned helplessness behaviors are independent of the presence or absence of hippocampal BDNF because blocking inescapable stress-induced BDNF suppression does not always prevent learned helplessness, and learned helplessness does not always occur in the presence of reduced BDNF. Results also suggest that the prevention of stress-induced hippocampal BDNF suppression is not necessary for the protective effect of wheel running against learned helplessness.

show abstract

“…It is well known that the serotonin reuptake inhibitor (SRI) class of antidepressants increase concentrations of serotonin in the synapse by blocking the serotonin transporter (5-HTT) (Blakely et al 1991;Ramamoorthy et al 1993). However, given the time lag between the initial inhibitory effects of antidepressants on the 5-HTT and an observable improvement in symptoms of depression, the mechanisms underlying the therapeutic effects of these drugs are likely to occur downstream of 5-HTT inhibition (Blier et al 1990;Chaput et al 1991;Duman 1998;Manji et al 2001). Another unresolved issue stems from the fact that antidepressants have differing affinity for the 5-HTT and even SRIs exert activity at other monoamine receptors and transporters (Stahl 1998).…”

mentioning

confidence: 99%

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Holmes

Yang

Murphy

et al. 2002

Neuropsychopharmacology

262

181

View full text Add to dashboard Cite

Inhibition of the serotonin transporter (5-HTT) is a principal initial target of many antidepressants. However, the contribution of the 5-HTT to their therapeutic efficacy is incompletely understood. We utilized a targeted gene mutation approach to examine the role of the 5-HTT in the behavioral actions of antidepressants. The 5-HTT mutation was bred onto two separate genetic backgrounds, C57BL/6J and 129S6. On a preliminary screen for gross physical, neurological and behavioral functions, all measures were normal with the exception that 5-HTT 5-HTT Ϫ / Ϫ mice on the C57BL/6J background showed no baseline antidepressant-related phenotype on either test. The behavioral effects of three antidepressants were tested in 5-HTT mutant mice (C57BL/6J background) in the tail suspension test. The anti-immobility effects of the serotonin reuptake inhibitor, fluoxetine (30 mg/kg), were abolished in 5-HTT Ϫ / Ϫ mice, confirming that the 5-HTT gene is required for the behavioral effects of fluoxetine. In contrast, 5-HTT Ϫ / Ϫ mice retained sensitivity to the anti-immobility effects of the norepinephrine reuptake inhibitor, desipramine (20 mg/kg), and the mixed serotonin/norepinephrine reuptake inhibitor, imipramine (25 mg/kg Antidepressants are thought to normalize the disturbances in monoamine function that occur in affective disorders (Feighner and Boyer 1996;Frazer 1997; Montgomery and Den Boer 2001). While dysfunctions in noradrenergic and dopaminergic systems are putative etiological factors in depression, there is considerable evidence indicating that perturbation of central serotonergic activity is a major etiological component of depression (Willner 1985;Murphy 1990;Maes and Meltzer 1995;Charney 1998 NO . 6 Antidepressant Responses in 5-HTT KO Mice 915 (for reviews see Brown and Linnoila 1990;Owens and Nemeroff 1998;Mann 1999). The serotonin transporter (5-HTT) acts as a key regulator of serotonin signaling. By regulating reuptake of released serotonin, the 5-HTT controls the duration and intensity of serotoninergic activity at the synapse. The 5-HTT has been directly implicated in depression by the finding that brain 5-HTT binding density is reduced in brains and platelets of depressed patients (e.g., Nemeroff et al. 1994;Malison et al. 1998;Mann et al. 2000). Moreover, a number of studies have found an association between genetic variation in the regulatory region of the 5-HTT gene and depression (e.g., Battersby et al. 1996; Collier et al. 1996a,b;Furlong et al. 1998;Rees et al. 1997;Menza et al. 1999; but see Seretti et al. 1999). The 5-HTT is also a major target for many antidepressant drug treatments (Blakely et al. 1991;Ramamoorthy et al. 1993). It is well known that the serotonin reuptake inhibitor (SRI) class of antidepressants increase concentrations of serotonin in the synapse by blocking the serotonin transporter (5-HTT) (Blakely et al. 1991;Ramamoorthy et al. 1993). However, given the time lag between the initial inhibitory effects of antidepressants on the 5-HTT and an observable improvement in sympt...

show abstract

Novel therapeutic approaches beyond the serotonin receptor

Cited by 233 publications

References 46 publications

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and Continuation Treatment of Major Depressive Disorder

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and Continuation Treatment of Major Depressive Disorder

Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

Contact Info

Product

Resources

About