The inhibitory effect of 8-OH-DPAT on the firing activity of dorsal raphe serotoninergic neurons in rats is attenuated by lesion of the frontal cortex

Ceci, Angelo; Baschirotto, A.; Borsini, Franco

doi:10.1016/0028-3908(94)90177-5

Cited by 121 publications

(67 citation statements)

References 8 publications

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“…Hence, this finding of an attenuated response in the corticosterone-treated animals is suggestive of a functional desensitization of these somatodendritic autoreceptors. A caveat to this conclusion is that DRN firing has also been shown to be under the inhibitory influence of 5-HT 1A receptors located in the prefrontal cortex (Ceci et al, 1994;Hajós et al, 1999). Since the agonist drug was administered systemically, it is possible that the change observed reflects an alteration in the sensitivity of postsynaptic 5-HT 1A receptors in addition to that of 5-HT 1A autoreceptors.…”

Section: Discussionmentioning

confidence: 99%

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

Leitch

Ingram

Young

et al. 2003

Neuropsychopharmacol

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Depression is associated with glucocorticoid abnormalities, in particular a flattening of the diurnal cortisol rhythm. Recent data suggest that an important factor in the aetiology of depression may be a deficit in the function and expression of 5-HT 1A receptors, which has been reported in depressed patients. The present study assessed the possibility that this cortisol abnormality is causal in the 5-HT 1A receptor deficits. First, a rat model of flattened glucocorticoid rhythm was developed. Controlled release corticosterone pellets implanted for 14 days flattened the corticosterone rhythm and maintained levels constant midway between the nadir and zenith levels observed in sham-operated rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus, the inhibitory response to 8-OHDPAT was measured to determine the sensitivity of somatodendritic 5-HT 1A autoreceptors. Corticosterone treatment was found to induce a significant attenuation in the response to 8-OHDPAT, indicating functional desensitization of somatodendritic 5-HT 1A autoreceptors. There was no effect of corticosterone treatment on basal extracellular 5-HT levels. The data suggest that the glucocorticoid abnormalities associated with depression may impact on the functioning of 5-HT 1A receptors in the brain. These findings suggest that resolution of cortisol abnormalities may be a valuable target for pharmacotherapy in the treatment of depression.

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Section: Discussionmentioning

confidence: 99%

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

Leitch

Ingram

Young

et al. 2003

Neuropsychopharmacol

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“…The pattern of response to antidepressant treatments acting through the modulation of 5-HT 1A -receptors may therefore depend on a few factors, such as the subtype of depressed patients, and the brain structures which are specifically involved (Borsini 1994;De Vry 1995). For example, the inhibitory effects of 8-OH-DPAT on 5-HT-neurons firing would involve a feedback loop activated by post-synaptic 5-HT 1A -receptors (Ceci et al 1994;Hajos et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test

Reneric

Bouvard

Stinus

2001

Neuropsychopharmacology

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The rat forced swimming test (FST) predicts the efficacy of antidepressants, which decrease immobility duration in the test, and can distinguish selective serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors, which, respectively, increase swimming and climbing behaviors. However, dual 5-HT and NA reuptake-inhibition produces climbing behavior solely, thereby suggesting with other data that the NA-system mediates inhibiting interactions on 5-HT-induced swimming in the FST. Since ␣ 2 -adrenoreceptors and 5-HT 1A -receptors have important regulatory functions and are involved in 5-HT/NA interactions, we examined whether the ␣ 2 -receptorantagonist idazoxan and the 5-HT 1A -receptor-agonist 8-hydroxy-2-(di-n -propylamino)-tetralin (8-OH-DPAT) would modify the behavioral pattern induced in the FST by either selective or non-selective antidepressant treatments. The rats were treated subacutely (3 injections IP over 48 h) with: (a) idazoxan (0.5-10 mg/kg) alone, and in combination with desipramine (10 mg/kg), or desipramine ϩ fluoxetine (10/10 mg/kg), or the dual serotonin/ noradrenaline reuptake-inhibitor milnacipran (20 mg/kg). (b) 8-OH- (Porsolt et al. 1977(Porsolt et al. , 1978(Porsolt et al. , 1979, which detects all the major classes of antidepressant treatments (Borsini and Meli 1988) NO . 4 (MAOIs), atypical antidepressants, and electroconvulsive shock. The FST is also used to investigate the mechanisms of action of antidepressant drugs (Borsini 1995) or the functional interactions that occur when antidepressants are administered (Redrobe and Bourin 1999;Rénéric and Lucki 1998). The rat FST consists of placing the animal in a jar filled with water for a pre-test on day 1, and for a five-minute test session 24 hours later, with the drugs being administered sub-acutely (3 injections) between the two sessions. The animal first attempts to escape and then progressively adopts an immobile posture, making only small movements to keep its head above water. Effective antidepressant treatments decrease the duration of immobility in the test session (Porsolt et al. 1978). Other methods of scoring the FST take into account swimming and climbing, two main active behaviors occurring in the test, which contribute to the antidepressant-like decrease in immobility-duration (Detke et al. 1995b). This procedure showed that noradrenaline (NA)-reuptake inhibitors (NRIs) and selective serotonin (5-hydroxytryptamine/ 5-HT)-reuptake inhibitors (SSRIs) increased selectively and respectively climbing and swimming behavior (Detke et al. 1995b). This technique can thus distinguish components to the behavioral response to antidepressants (Lucki 1997), which is in agreement with distinguishable neurochemical and behavioral contributions to the therapeutic effects of antidepressants in humans (Heninger et al. 1996;Katz et al. 1994).Serotonin and noradrenaline systems are directly involved in the pathogenesis and the recovery from depression (Blier et al. 1990;Caldecott Hazard et al. 1991), and there were clinical suggestions that...

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“…However, several areas rich in a 1 -and a 2 -adrenoceptors projecting to the lateral habenula, such as the hippocampus or the amygdala (Matthews-Felton et al, 1999), contain a high density of both a-adrenoceptor families. Likewise, all cortical layers in the frontal cortex contain a moderate to high density of a-adrenoceptors (Unnerstall et al, 1984;Pieribone et al, 1994;Rosin et al, 1996;Day et al, 1997;Winzer-Serhan et al, 1997a,b) that could be involved in the distal control of serotonergic activity and 5-HT release, as shown for cortical (prefrontal) 5-HT 1A and 5-HT 2A receptors (Ceci et al, 1994;Hajós et al, 1999;Celada et al, 2001;Martín-Ruiz et al, 2001a;Martín-Ruiz and Ugedo, 2001). Likewise, the medial prefrontal cortex controls the activity of locus coeruleus noradrenergic neurons (Jodo et al, 1998), which in turn might affect 5-HT neurons in the DR.…”

Section: Modulation Of 5-ht Release By A-adrenoceptorsmentioning

confidence: 98%

Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors

Bortolozzi

Artigas

2002

Neuropsychopharmacol

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The interactions between the brainstem serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic (NA) systems are important for the pathophysiology and treatment of affective disorders. We examined the influence of a-adrenoceptors on 5-HT and NA release in the rat dorsal raphe nucleus (DR) using microdialysis. 5-HT and NA concentrations in DR dialysates were virtually suppressed by TTX and increased by veratridine. The local and systemic administration of the a 1 -adrenoceptor antagonist prazosin reduced the DR 5-HT output but not that of NA. The maximal 5-HT reduction induced by local prazosin administration (À78% at 100 mM) was more marked than by its systemic administration (À43% at 0.3 mg/kg). The local application of NA and desipramine, to increase the tone on DR a 1 -adrenoceptors, did not enhance 5-HT release. The local (100 mM) or systemic (0.1-1 mg/kg s.c.) administration of clonidine reduced 5-HT and NA release (À48 and À79%, respectively, at 1 mg/kg), an effect reversed by RX-821002, which by itself increased both amines when given systemically. DSP-4 pretreatment prevented the effects of clonidine on 5-HT, suggesting the participation of a 2 -adrenoceptors on NA elements. Moreover, the systemic effect of clonidine on 5-HT (but not NA) was cancelled by lesion of the lateral habenula and by anesthesia, and was slightly enhanced by cortical transection. These data support the view that a 1 -adrenoceptors in the DR tonically stimulate 5-HT release, possibly at nearly maximal tone. Likewise, the 5-HT release is modulated by a 2 -adrenoceptors in NA neurons and in forebrain areas involved in the distal control of 5-HT neurons.

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The inhibitory effect of 8-OH-DPAT on the firing activity of dorsal raphe serotoninergic neurons in rats is attenuated by lesion of the frontal cortex

Cited by 121 publications

References 8 publications

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test

Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors

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