The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine

Samanin, R.; Ghezzi, D.; Valzelli, L.; Garattini, Silvio

doi:10.1016/0014-2999(72)90097-0

Cited by 143 publications

(24 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The brain serotonergic system originates from raphe nuclei in the brainstem [14]. Lesions of these nuclei induce hyperphagia [27] and interfere with the anorectic effect of fenfluramine [28]. The latter finding demonstrates that fenfluramine requires an intact brain serotonergic system to exert its anorectic effect.…”

mentioning

confidence: 98%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

259

167

View full text Add to dashboard Cite

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

show abstract

mentioning

confidence: 98%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

259

167

View full text Add to dashboard Cite

show abstract

“…Moreover, electrolytic lesions of the midbrain raphe nuclei, an important site of origin of 5-HT neurons in the brain (Dahlstrom and Fuxe, 1964), abolished the anorexia produced by fenfluramine (Samanin et al, 1972 Table 1 Percent responding on the fenfluramine lever as a function of dose of clnanserln (CIN), administered 30 minutes following Injection of 2 mg/kg fenfluramine and 30 minutes prior to testing. Each point represents the mean ± 1 SEM for 10 rats, "a" and "b" denote values that differ significantly (one-tailed; p 0.05; Student's t-test) from the 2 mg/kg fenfluramine and sallna groups respectively.…”

mentioning

confidence: 99%

Discriminative stimulus properties of fenfluramine: Evidence for serotonergic involvement

Mcelroy

Feldman

1984

Psychopharmacology

View full text Add to dashboard Cite

“…Based on this finding, it seems possible to rule out for mazindol-induced anorexia, the same mechanism of action suggested for fenfluramine (Funderburk et al, 1971;Samanin et al, 1972;Jespersen & Scheel-Kriuger, 1973;Clineschmidt, 1973). In conclusion, mazindol, although having a behavioural profile similar to that of (+)-amphetamine (Zambotti et al, 1975) shows some differences in its neurochemical effects.…”

Section: Resultsmentioning

confidence: 53%

“…Considerable evidence suggests that the anorectic effect of (+)-amphetamine is mediated by interactions with brain catecholamines (Weissman, Koe & Tenen, 1966;Holtzmann & Jewett, 1971; Schulz & Frey, 1972;Kruk, 1973; Barzaghi & Mantegazza, 1973a;Groppetti, Zambotti, Biazzi & Mantegazza, 1973b; Leibowitz, 1975), while fenfluramine, although chemically related to (+)-amphetamine, induces anorexia via direct or indirect indoleamine-like effects (Funderburk, Hazelwood, Ruckart & Ward, 1971;Samanin, Ghezzi, Valzelli & Garattini, 1972;Clineschmidt, 1973;Jespersen & Scheel-Kriiger, 1973).…”

Section: Introductionmentioning

confidence: 99%

Effects of Mazindol, a Non‐phenylethylamine Anorexigenic Agent, on Biogenic Amine Levels and Turnover Rate

Carruba¹,

Groppetti²,

Mantegazza³

et al. 1976

British J Pharmacology

View full text Add to dashboard Cite

I Mazindol is a new anorexigenic agent which possesses a different chemical structure from that of phenylethylamines, but shows a pharmacological profile similar to that of (+)-amphetamine. 2 Mazindol neither altered whole brain monoamine levels (noradrenaline (NA), dopamine, 5-hydroxytryptamine (5-HT)) nor changed NA levels in the hypothalamus or dopamine levels in the caudate nucleus.3 Mazindol enhanced dopamine turnover rate in the caudate nucleus, as shown by the increased rate of dopamine decline after blockade of catecholamine synthesis by a-methyl-p-tyrosine and decreased the conversion index of [3H1-tyrosine into brain NA. 4 Mazindol administration did not modify pargyline-induced decline of 5-hydroxyindoleacetic acid suggesting that 5-HT turnover is not altered by this drug.

show abstract

The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine

Cited by 143 publications

References 16 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Discriminative stimulus properties of fenfluramine: Evidence for serotonergic involvement

Effects of Mazindol, a Non‐phenylethylamine Anorexigenic Agent, on Biogenic Amine Levels and Turnover Rate

Contact Info

Product

Resources

About