Pharmacological profile of a model for central serotonin receptor activation

Matthews, William D.; Smith, Cynthia D.

doi:10.1016/0024-3205(80)90042-9

Cited by 66 publications

(25 citation statements)

References 17 publications

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“…5HT agonists adminis tered to rats induce head-twitch behavior (3,4). These facts are consistent with the observations that sCT influences the release of hormones from the hypophysis (5)(6)(7)(8), in duces anorexia (9), depresses the amphet amine-induced locomotor activity (10) and potentiates the head-twitch behavior elicited by 5-hydroxytryptophan (11).…”

supporting

confidence: 87%

Relationships between the effects of peripherally administered salmon calcitonin on calcaemia and brain biogenic amines.

1989

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Abstract-The effects of s.c. administered salmon calcitonin on the biogenic amine neurotransmitters and metabolites were studied in discrete brain sections in order to evaluate the relationships between these central effects and the fall of serum calcium and to investigate the mechanisms of calcitonin-induced behavioral changes.The biogenic amines and metabolites were simultaneously determined by high-performance liquid chromatography with electrochemical detection in tissue samples obtained from rats treated with 10-80 MRC U/kg of the peptide. Some rats were pretreated with calcium lactate to inhibit the calcitonin-induced hypo calcaemia.Most of the effects, consisting of signs of serotonergic system activation, have been observed in the hypothalamus, accounting for some behavioral effects of the peripherally administered salmon calcitonin. It was speculated that the acti vation of the brain serotonergic system could result from two indirect and separate mechanisms: the first, which would involve enhanced serotonin synthesis, seemed to be facilitated by calcium availability.A second possible mechanism, which would involve enhanced serotonin release from the neurons, seemed to be mediated by the fall of calcium levels in the blood.

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supporting

confidence: 87%

Relationships between the effects of peripherally administered salmon calcitonin on calcaemia and brain biogenic amines.

1989

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“…Possible reasons for this are differing pretreatment periods, and agonists and injection routes employed for inducing head-twitch responses in the mice. Mathews and Smith (1980) failed to alter 5-HTP "wet-dog" shakes in rats using WB4101 (2-(2,6-dimethoxy-phenylethyl) aminomethyl-l,4-benzodioxane). However, the specificity of WB4101 as an cq-adrenoceptor antagonist has been questioned (Massingham et al 1981;Palacios 1983).…”

Section: Discussionmentioning

confidence: 93%

“…The effects of ~-and a2-adrenoceptor agonists are, however, more controversial and although several studies have reported that ~2-adrenoceptor agonists are potent inhibitors of head-shake responses in mice and rats (Bednarczyk and Vetulani 1978;Vetulani et al 1980;Handley and Brown 1982), Bedard and Pycock (1977) have suggested that these drugs have no effect on this response. The el-adrenoceptor antagonists have similarly been reported to inhibit (Handley and Brown 1982) or alternatively, to have no effect (Mathews and Smith 1980) on 5-HTz-mediated behavioural responses. In view of this, the effects of manipulating central noradrenergic function on 5-HT2-mediated head-twitch responses in mice has now been thoroughly examined using selective a-and fl-adrenoceptor drugs and noradrenergic lesioning techniques.…”

mentioning

confidence: 90%

The influence of central noradrenergic function on 5-HT2-mediated head-twitch responses in mice: Possible implications for the actions of antidepressant drugs

et al. 1986

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This study has investigated the influence of central noradrenergic function on 5-HT2-mediated head-twitch responses in mice. Central injection of low doses of the alpha 1-adrenoceptor agonists phenylephrine or methoxamine, or peripheral administration of the antagonist prazosin had no effect on the head-twitches induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). High doses of both alpha 1-adrenoceptor agonists and antagonists markedly inhibited this response. Head-twitches induced by 5-MeODMT were potently inhibited by low doses of the alpha 2-adrenoceptor agonist clonidine, and potentiated by the antagonists idazoxan and yohimbine. Clonidine also potently inhibited this response when produced by 5-hydroxytryptophan (5-HTP) and carbidopa. The action of the beta-adrenoceptor agonist clenbuterol on head-twitches was paradoxical, this drug enhancing the responses to precursor loading (5-HTP/carbidopa) but inhibiting those induced by direct agonists (5-MeODMT, quipazine). Lesioning noradrenergic neurons by central injection of 6-hydroxydopamine (6-OHDA) or peripheral administration of DSP-4 resulted in enhanced head-twitch behaviour. 6-Hydroxydopamine lesioning did not alter the inhibition of head-twitch responses by clonidine but prevented their enhancement following withdrawal from repeated desmethylimipramine (DMI) administration. It is therefore suggested that head-twitch behaviour may be under tonic control by a population of alpha 2-adrenoceptors which are not on presynaptic noradrenergic terminals, but are postsynaptic and located "down-stream" of the 5-HT2 receptor. In addition, the enhancement of this behaviour produced by withdrawal from repeated DMI administration probably also resulted from alterations in central noradrenergic function.

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“…Head twitches were chosen as they are a quantifiable and reliable measure of serotonergic activation: the response is dose-related and appears even in the presence of low doses of 5-HT agonists (4). Male Sprague Dawley rats (Nossan, Milano, Italy) weighing 250-300 g were used.…”

mentioning

confidence: 99%

Salmon calcitonin induced head twitch in the rat.

Gaggi

Iasio

1988

Jpn.J.Pharmacol

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Abstract-The intracerebroventricular administration of salmon calcitonin (sCT) to rats induced a dose-dependent increase in the number of head twitches and poten tiated such a response elicited by L-5-hydroxytryptophan (L-5-HTP). Subcu taneously administered sCT was ineffective "per se" but could again potentiate the head twitch response elicited by L-5-HTP.Since these data suggest a stimulation of the brain serotonergic pathways, the obtained results support the hypothesis that some central actions of sCT may involve activation of serotonergic systems in the rat brain.should enhance this increase. Head twitches were chosen as they are a quantifiable and reliable measure of serotonergic activation: the response is dose-related and appears even in the presence of low doses of 5-HT agonists (4). Male Sprague Dawley rats (Nossan, Milano, Italy) weighing 250-300 g were used. They were housed under con trolled conditions of light (7.00 a.m.-7.00 p.m.), temperature (22+2°C) and humidity (65%) and were allowed free access to standard laboratory diet and tap water. sCT was kindly supplied by Sandoz (Basel) as commercial vials (containing 100 MRCU=20 ug of peptide, 2 mg of acetic acid, 2 mg of sodium acetate, 7.5 mg of sodium chloride and distilled water to 1 ml volume) and as pure powder. As needed, these vials were diluted with saline, and sCT was s.c. injected at the doses of 5, 10, 20, 40 and 80 /ig/kg; control rats received 4 ml/kg of saline containing ace tic acid. I.c.v. injected rats were implanted, at least 7 days before the behavioral trials, with permanent plastic cannulae entering the right ventricle. By this route, the powder form of sCT dissolved in sterile saline containing 0.5% human albumin was administered at the doses of 0.1, 0.2, 0.4 and 0.8 ug/rat; control animals received only vehicle (20 al/rat). Immediately after treatment, the rats were put into transparent plexiglas cylinders (20 cm diameter, 25 cm height), and 30 min later, the head-twitches exhibited by the animals

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Pharmacological profile of a model for central serotonin receptor activation

Cited by 66 publications

References 17 publications

Relationships between the effects of peripherally administered salmon calcitonin on calcaemia and brain biogenic amines.

Relationships between the effects of peripherally administered salmon calcitonin on calcaemia and brain biogenic amines.

The influence of central noradrenergic function on 5-HT2-mediated head-twitch responses in mice: Possible implications for the actions of antidepressant drugs

Salmon calcitonin induced head twitch in the rat.

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