5-Hydroxytryptamine pathways in anxiety and its treatment

Handley, Sheila L.

doi:10.1016/0163-7258(95)00004-z

Cited by 202 publications

(95 citation statements)

References 253 publications

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“…Thus, it is perhaps not surprising that chronic SCIT treatment did not prevent the CUS-induced increase in anxiety-like behavior on the plus-maze in the present study, nor that SCIT treatment alone had a modest anxiogenic effect. As SSRIs are clearly effective in treating human anxiety, one obvious implication from this literature, as well as the present study, is that many commonly used assays of anxiety-like behavior in rats are not valid models of human anxiety disorders that are responsive to SSRI treatment (eg, see Handley, 1995;Handley and McBlane, 1993).…”

Section: Discussionmentioning

confidence: 73%

“…The results of numerous preclinical experiments testing the effects of 5-HT-related drugs in general, and SSRIs in particular, in various animal models of anxiety have been equivocal at best (see Griebel, 1995;Griebel et al, 1997;Handley, 1995). In the elevated plus-maze and related tests (eg, social interaction), both acute and chronic treatment with SSRIs have typically had no effect, or have had anxiogenic effects (File et al, 1999;Silva and Brandão, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

344

263

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Chronic stress is a risk factor for the development of many psychopathological conditions in humans, including major depression and anxiety disorders. There is a high degree of comorbidity of depression and anxiety. Moreover, cognitive impairments associated with frontal lobe dysfunction, including deficits in cognitive set-shifting and behavioral flexibility, are increasingly recognized as major components of depression, anxiety disorders, and other stress-related psychiatric illnesses. To begin to understand the neurobiological mechanisms underlying the cognitive and emotional consequences of chronic stress, it is necessary to employ an animal model that exhibits similar effects. In the present study, a rat model of chronic unpredictable stress (CUS) consistently induced a cognitive impairment in extradimensional set shifting capability in an attentional set shifting test, suggesting an alteration in function of the medial prefrontal cortex. CUS also increased anxiety-like behavior on the elevated plus-maze. Further, chronic treatment both with the selective norepinephrine reuptake blocker, desipramine (7.5 mg/kg/day), and the selective serotonin reuptake blocker, escitalopram (10 mg/kg/ day), beginning 1 week before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced deficit in extradimensional set-shifting. Chronic desipramine treatment also prevented the CUS-induced increase in anxiety-like behavioral reactivity on the plus-maze, but escitalopram was less effective on this measure. Thus, CUS induced both cognitive and emotional disturbances that are similar to components of major depression and anxiety disorders. These effects were prevented by chronic treatment with antidepressant drugs, consistent also with clinical evidence that relapse of depressive episodes can be prevented by antidepressant drug treatment.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

344

263

View full text Add to dashboard Cite

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“…1 5-HT 1A receptor agonists have an anxiolytic effect, as demonstrated in human and animal studies. 40 The present study focused on the sympathoexcitatory response evoked by activation of DMH neurons, but our results also raise the important question as to whether other stress-induced responses that are mediated by the DMH, including respiratory effects and hormonal responses such as the release of ACTH, 2 may also be suppressed by administration of 5-HT 1A receptor agonists. In addition, a further question is whether the suppression of the DMH-evoked sympathoexcitatory response is specific to that particular nucleus or alternatively is a general effect on sympathoexcitatory responses evoked by activation of other hypothalamic nuclei, such as the paraventricular nucleus, which also play a role in mediating stress-induced responses.…”

Section: Perspectivesmentioning

confidence: 99%

Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

2005

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Abstract-The dorsomedial hypothalamic nucleus is a key component of the central pathways subserving the cardiovascular response to psychological stress, which is believed to be an important risk factor for hypertension. Previous studies indicate that 5-hydroxytryptamine 1A receptors can modulate the cardiovascular responses associated with stress. In this study, we determined in anesthetized rats the effects of systemic or intracisternal administration of 8-hydroxy-2-(di-npropylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors, and then subsequent administration of the selective antagonist WAY-100635 on the cardiovascular response evoked by activation of the dorsomedial hypothalamic nucleus (by microinjection of bicuculline). The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n-propylamino)tetralin and then completely restored by subsequent administration of WAY-100635, whether administered systemically or intracisternally. In contrast, systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no significant effect on the baseline level or reflex changes in RSNA evoked by chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction ( Key Words: Ⅲ hypothalamus Ⅲ stress Ⅲ baroreflex Ⅲ chemoreceptors P sychological stress is believed to be an important risk factor for hypertension and other cardiovascular disorders. 1 Studies in conscious and anesthetized rats have demonstrated that the dorsomedial hypothalamic nucleus (DMH) plays a critical role in mediating the autonomic, neuroendocrine, and behavioral response to psychological stress, such as air jet stress. 2 Activation of neurons in the DMH evokes anxiety-like behavior associated with a wide range of autonomic and hormonal responses, including increases in heart rate (HR; mediated via an increase in cardiac sympathetic nerve activity 3,4 ), renal sympathetic nerve activity (RSNA), gastrointestinal motility, and in the secretion of adrenomedullary hormones and adrenocorticotropic hormone (corticotropin [ACTH]). 2-8 Conversely, bilateral microinjections into the DMH of muscimol (a ␥-aminobutyric acid type A [GABA A ] receptor agonist) or of kynunerate (an antagonist of ionotropic glutamate receptors) greatly reduces the increases in arterial pressure, HR, ACTH secretion, and anxiety-like behavior normally evoked by air jet stress. 8 -10 It has been shown recently that the DMH also plays an important role in generating thermoregulatory responses.Activation of neurons in the DMH evokes an increase in the activity of sympathetic nerves innervating brown adipose tissue (BAT), accompanied by increases in BAT temperature and end-tidal CO 2 , 3 as well as cutaneous vasoconstriction. 11 These thermoregulatory effects may also be part of a stress response because an increase in body temperature can be induced by stress (so-cal...

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“…Others, though, consider that even if there is some constant tonic level of serotonergic activity, there can still be local modulation of serotonin release that may be both brain region and stimulus specific (Kirby et al, 1995(Kirby et al, , 1997. From a behavioral perspective, the activation of serotonergic neurons has been hypothesized to produce behavioral inhibition (Soubrié, 1986;Spoont, 1992;Handley, 1995), that is, serotonin may promote response suppression, inhibition, passivity, and waiting. More specifically at the behavioral level, it has been associated with the regulation of impulsivity (Soubrié, 1986), aggression (Linnoila et al, 1983), and anxiety (Briley and Chopin, 1991).…”

Section: Drug-induced Effects On Monoamines and Behavioral Changesmentioning

confidence: 99%

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Katz

Tekell

Bowden

et al. 2003

Neuropsychopharmacol

232

153

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This study was aimed at resolving the time course of clinical action of antidepressants (ADs) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients. The first goal was to identify, during the first 2 weeks of treatment, the onset of clinical actions of the selective serotonin reuptake inhibitor (SSRI), paroxetine, and the selective noradrenergic reuptake inhibitor, desipramine (DMI). The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients. The design was a randomized, parallel group, placebo-controlled, double-blind study for 6 weeks of treatment following a 1-week washout period. The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity. The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days, averaged 13 days for paroxetine, and was 16-42 days for placebo. Furthermore, as hypothesized, the different types of ADs initially impacted different behavioral aspects of the disorder. After 1 week of treatment, DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo, and this difference persisted at the second week of treatment. Early improvement in depressed mood-motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not. Paroxetine initially reduced anxiety more in responders than in nonresponders, and by the second week, significantly improved depressed mood and distressed expression in responders to a greater extent. Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement. Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs, results that could eventually be applied directly to clinical practice.

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5-Hydroxytryptamine pathways in anxiety and its treatment

Cited by 202 publications

References 253 publications

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

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