Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function

Garratt, Jeni C.; Crespi, Francesco; Mason, Robert J.; Marsden, C.A.

doi:10.1016/0014-2999(91)90204-4

Cited by 55 publications

(34 citation statements)

References 18 publications

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“…These results, however, are not in agreement with the previous finding that the a2-adrenoceptor antagonist, idazoxan, increased 5-HIAA levels in the hypothalamus and dorsal raphe nucleus (Garratt et al, 1991). The difference could be the result of a discrepancy between the different methods used.…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, therefore, the increases in the extracellular 5-HT levels induced by administration of yohimbine could be the result of blockade of an inhibitory noradrenergic innervation located on the 5-HT nerve terminals in the forebrain or 5-HT cells in the midbrain. This hypothesis is supported by data showing that the injection of the a2-adrenoceptor antagonist, idazoxan into the dorsal raphe nucleus caused an elevation of the firing rate of 5-HT neurones in the dorsal raphe (Freeman, & Aghajanian, 1984), and systemic administration of idazoxan increased the extracellular levels of 5-HT and 5-HIAA in the rat frontal cortex (Garratt et al, 1991).…”

Section: Discussionmentioning

confidence: 81%

See 1 more Smart Citation

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

Cheng

Costall

Jin

et al. 1993

British J Pharmacology

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1 The interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5-hydroxytryptamine (5-HT) release in the frontal cortex of the freely-moving rat was assessed using the microdialysis technique.2 The a2-adrenoceptor antagonist, yohimbine (5.0 mg kg-', i.p.) increased maximally the extracellular levels of 5-HT in the rat frontal cortex by approximately 230% of the basal levels. failed to modify the response to yohimbine. 6 The present study provides evidence of the ability of the anxiogenic agent, yohimbine, to increase the activity of the central 5-hydroxytryptaminergic system and the ability of clonidine and various anxiolytic and putative anxiolytic agents to prevent the yohimbine response.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 81%

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

Cheng

Costall

Jin

et al. 1993

British J Pharmacology

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“…There is evidence for the existence of two of these subtypes in rat brain, namely x2A/D and a2C (Lorenz et al, 1990;Uhlen et al, 1992;MacKinnon et al, 1992); they have different anatomical distributions (Wamsley et al, 1992), which may suggest heterogeneous expression on neurones of different neurotransmitter identities. Indeed, as well as presynaptic autoreceptors on noradrenergic neurones, which are believed to be of the a2D subtype in the rat cortex (Trendelenburg et al, 1993), there are also a2-adrenoceptors on 5-hydroxytryptamine (5-HT) cell bodies and terminals which mediate tonic inhibitory influences of noradrenaline on 5-HT neurotransmission (Garratt et al, 1991;Tao & Hjorth, 1992;Rosin et al, 1993;Feuerstein et al, 1993). Although these are distinct from the a2Ax subtype, their precise identity is still unclear (Maura et al, 1992;Gobbi et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

A re‐evaluation of the role of α₂‐adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat

Redfern

Williams

1995

British J Pharmacology

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1 The acute behavioural effects of the a2-adrenoceptor antagonists, yohimbine, idazoxan and delequamine (RS-15385-197) were compared in two tests of exploratory behaviour in the rat, operated in tandem. These were the elevated X-maze test (5 min) and a modified holeboard test (12 min), which comprised a holeboard arena with a small roof in one corner as a 'refuge'. Rats were first placed into this corner, thus enabling measurements of initial emergence latency and the number of forays. The experiments were always done with a concomitant vehicle control group, with 10-12 rats per group, and with the treatment blinded. 2 In order to validate the tests, the effects of representatives of four classes of psychoactive agents were examined, viz. picrotoxin (anxiogenic), chlordiazepoxide (anxiolytic), (+)-amphetamine (stimulant) and diphenhydramine (sedative). The modified holeboard tended to be more sensitive than the measurement of total arm entries in the elevated X-maze at detecting drug effects on exploratory behaviour, but unlike the X-maze it could not clearly identify each class of agent. Thus, picrotoxin (5 mg kg-', i.p.) reduced total arm entries and open arm exploration in the X-maze (P<0.02) and suppressed most measures of activity in the holeboard (P<0.05); chlordiazepoxide (7.5 mg kg-1, i.p) increased total arm entries and open arm exploration (P<0.02) in the X-maze, without clear-cut effects in the holeboard; (+)-amphetamine (1 mg kg-, i.p.) had no significant effects in the X-maze, but increased most holeboard activities (P<0.05), and diphenhydramine (30 mg kg-', i.p.) reduced total arm entries in the X-maze (P<0.002) and hole exploration in the holeboard (P<0.05). 3 The actions of yohimbine most closely resembled those of picrotoxin. In the elevated X-maze, yohimbine (3 mg kg , i.p.) decreased the total number of arm entries (P<0.02); a larger dose (10 mg kg-', i.p.) also reduced time spent on the open arms (P<0.02). In contrast, delequamine (3 mg kg-, i.p.) and idazoxan (3 mg kg-', i.p.) had no effect. 4 In the partially-shaded holeboard, yohimbine (3 mg kg-', i.p.) suppressed hole exploration (P<0.05); a higher dose (10 mg kg-', i.p.) increased emergence latency (P<0.002) and virtually abolished all activity. Delequamine (3 mg kg-, i.p.) and idazoxan (3 mg kg-', i.p.) did not influence emergence latency or holeboard activities.5 The extent of the blockade of central a2-adrenoceptors achieved during the tests was assessed by the ability of the doses used to reverse mydriasis induced by clonidine (300 Ag kg-', s.c.) in anaesthetized rats. At a dose of 3 mg kg-, i.p., delequamine and idazoxan produced a rapid, sustained reversal of the clonidine response (by 87 ±2 and 86 ± 2% respectively, 30 min after injection) whereas yohimbine produced a partial reversal of only 43 ± 13%. The higher dose of yohimbine used in the exploratory tests (10 mg kg'-, i.p.) was required in order to achieve 77 ± 4% reversal of clonidine-induced mydriasis.6 We therefore conclude that blockade of central a2-adrenoceptors per se...

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“…This agent could conceivably enhance serotonergic transmission through the removal of a self-inhibitory effect of NA on noradrenergic terminals in the DR, thus increasing the release of NA (Figure 4d) and hence the tone on postsynaptic a 1 -adrenoceptors. Indeed, the systemic and intra-raphe administration of idazoxan, another a 2 -adrenoceptor antagonist, increased the firing rate of 5-HT neurons in the DR (Garratt et al, 1991;Hertel et al, 1997). Although this possibility cannot be fully discarded, it seems unlikely in view of the different temporal profile of 5-HT and NA changes after systemic RX 821002 administration (Figures 4c and d).…”

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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Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function

Cited by 55 publications

References 18 publications

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

A re‐evaluation of the role of α₂‐adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat

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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Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function

Cited by 55 publications

References 18 publications

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

A re‐evaluation of the role of α2‐adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat

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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A re‐evaluation of the role of α₂‐adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat