The effects of acute and repeated administration of various antidepressant drugs on clonidine-induced hypoactivity in mice and rats

Heal, David J.; Lister, S. J. S.; Smith, Sharon L.; Davies, Cledwyn L.; Molyneux, Stephen G.; Green, A.R.

doi:10.1016/0028-3908(83)90214-9

Cited by 60 publications

(24 citation statements)

References 26 publications

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“…Since the difference was observed for ECS, as well as for DMI, then this was unlikely to be due to pharmacokinetic effects. Furthermore, Heal et al (1983) have previously shown that there is no correlation between the attenuation of clonidine-induced hypoactivity and plasma DMI concentrations. Another possible explanation for this dissimilarity between the sexes is that clonidine had to be given at a higher dose to the females to induce the same degree of hypoactivity.…”

Section: Discussionmentioning

confidence: 97%

“…However, presynaptic x2-adrenoceptor func-1 Author for correspondence. tion is also decreased by repeated administration of desipramine (DMI;Tang et al, 1979;McMillen et al, 1980;Sugrue, 1983;Heal et al, 1983;1987a) and ECS (Heal et al, 1981;1987a;Sugrue, 1983). Several groups have also shown that postsynaptic a2-adrenoceptors are decreased by repeated ECS (Stanford & Nutt, 1982;Pilc & Vetulani, 1982;Heal et al, 1987a), but the effect of chronic DMI treatment is much more controversial (Johnson et al,function which are produced by DMI and ECS treatment are markedly influenced by the circulating levels of oestradiol (Bristow et al, 1986;Heal et al, 1988) and the thyroid hormone, triiodothyronine (T3; Heal et al, 1987a).…”

Section: Introductionmentioning

confidence: 99%

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Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Heal

Bristow

Hurst

et al. 1989

British J Pharmacology

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1 Clonidine induces hypoactivity in rodents. Male rats were found to be markedly more susceptible to the sedative effects of this a2-adrenoceptor agonist than females. Thus to obtain identical hypoactivity responses for subsequent experiments, clonidine was administered to male and female rats at doses of 0.2 and 0.5 mg kg-1, respectively. 2 The clonidine-induced hypoactivity response of female rats was not affected by the oestrous cycle. 3 Repeated injection of desipramine (DMI; 5mg kg-1 b.d.) for up to 14 days progressively attenuated clonidine-induced hypoactivity in both male and female rats. However, in males the attenuation was more rapid in onset and a greater overall reduction was obtained. This a2-adrenoceptor-mediated response was also progressively reversed by repeated daily administration of an electroconvulsive shock (ECS; 110 V, 1 s). In this case, although the maximum decrease was greater in males, the time of onset was identical in both sexes.4 There were no sex-related differences in either the number or affinity of a2-and ,B-adrenoceptors in rat cortex. Cortical a2-adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS x 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical fi-adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS x 10, but not ECS x 2. 5 Viewed overall, the data show differences in a2-adrenoceptor function between the sexes, as determined by clonidine-induced hypoactivity and the responsiveness of this paradigm to repeated administration of DMI and ECS. In contrast, no differences were observed in complementary a2-and /-adrenoceptor binding experiments using rat cortical tissue.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Heal

Bristow

Hurst

et al. 1989

British J Pharmacology

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“…A more marked attenuation of these responses was observed, however, at 18-21 h after withdrawal from chronic DMI treatment, whereas no effect was seen 18-21 h after a single dose of DMI. Heal et al (1983) found similar actions of acute and repeated DMI administration on the hypoactivity induced in both mice and rats by clonidine. The use of UK-14,304 as an agonist in these models may have certain advantages over that of clonidine.…”

Section: Resultsmentioning

confidence: 52%

“…Other studies using biochemical and electrophysiological (McMillen et al, 1980), behavioural (Spyraki & Fibiger, 1980;Heal et al, 1983) and physiological (Gorka & Zacny, 1981) techniques have also demonstrated a decrease in the sensitivity of central a2-adrenoceptors after long term NA re-uptake inhibition. Furthermore, several other types of antidepressant therapy, such as repeated ECT (Heal et al, 1981) and chronic treatment with the monoamine oxidase inhibitor, clorgyline (Aulakh et al, 1983), have also been reported to decrease the function of Oe2-adrenoceptors.…”

Section: Resultsmentioning

confidence: 91%

“…The development of CX2-adrenoceptor subsensitivity has been indicated by the finding that chronic, but not acute treatment, with the noradrenaline (NA) uptake inhibitor desipramine (DMI) attenuates the abilities of clonidine to inhibit NA turnover in rat brain (McMillen et al, 1980;Sugrue, 1981) and to induce sedation in rodents (Spyraki & Fibiger, 1980;Heal et al, 1983). Although a decrease in a2-autoreceptor sensitivity is thought to be responsible for the former 'Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

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The effects of acute and chronic desipramine on the thermogenic and hypoactivity responses to α₂‐agonists in reserpinized and normal mice

Bill¹,

Hughes²,

Stephens³

1989

British J Pharmacology

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1 The effects of acute and chronic (14 day) administration of the noradrenaline uptake inhibitor, desipramine (DMI), on the thermogenic responses to clonidine in reserpine-treated mice, and on the hypothermic and hypoactivity responses to the a2-agonist, UK-14,304, in untreated mice were examined. 2 Taking the capacity of DMI to delay the onset of reserpine-induced hypothermia as an indicator of noradrenaline (NA) uptake inhibition, the lowest dose of DMI to inhibit uptake significantly for 12 h in the mouse was shown to be between 10 and 20mg kg-1 orally. 3 Chronic (every 12h for 14 days), but not acute treatment with DMI (15mgkg-1, orally), attenuated the thermogenic responses to low doses (0.02-0.225mg kg 1, i.p.) of clonidine (injected 20 h after the last dose of DMI) in reserpinized mice. 4 Acute DMI administration slightly attenuated the hypothermia and hypoactivity induced by UK-14,304 (0.25-1.Omgkg-', i.p.) when injected 2h, but not when injected 18-21h before the agonist. In contrast, 18-21 h after withdrawal from chronic DMI both of these responses to UK-14, 304 were markedly attenuated. 5 As the thermogenic response to clonidine in reserpinized mice appears to involve central postsynaptic a2-adrenoceptors, these results suggest that prolonged inhibition of NA uptake decreases the sensitivity of postsynaptic CX2-adrenoceptors. The results of the studies using UK-14,304 indicate that central aC2-adrenoceptors involved in mediating other behavioural and pharmacological responses to a2-agonists are also down-regulated by chronic inhibition of NA uptake.

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Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression

Miller

Delgado²,

Salomon³

et al. 1996

Arch Gen Psychiatry

170

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The therapeutic effects of norepinephrine reuptake inhibitors, but not serotonin reuptake inhibitors, are reversed by catecholamine depletion. Considered with previous reports that serotonin depletion produces depressive relapses in patients in remission maintained with serotonin reuptake inhibitors, but not norepinephrine reuptake inhibitors, these findings suggest that antidepressants may not work via a single monoamine-related mechanism.

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The effects of acute and repeated administration of various antidepressant drugs on clonidine-induced hypoactivity in mice and rats

Cited by 60 publications

References 26 publications

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

The effects of acute and chronic desipramine on the thermogenic and hypoactivity responses to α₂‐agonists in reserpinized and normal mice

Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression

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The effects of acute and repeated administration of various antidepressant drugs on clonidine-induced hypoactivity in mice and rats

Cited by 60 publications

References 26 publications

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Sex‐related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

The effects of acute and chronic desipramine on the thermogenic and hypoactivity responses to α2‐agonists in reserpinized and normal mice

Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression

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The effects of acute and chronic desipramine on the thermogenic and hypoactivity responses to α₂‐agonists in reserpinized and normal mice