title: Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications.
abstract: This minireview deals with the possible roles of monoamines in feeding and feeding disorders. The introduction sketches the results of earlier studies with local drug injections and selective neurotoxins which provided pharmacological evidence that monoamines can influence food intake and body weight. A table summarizing this evidence is used to list monoamine changes that could underlie anorexia or hyperphagia. It is apparent that abnormalities in the monoamines, along with their cotransmitters, could cause many forms of feeding disorder. It is proposed as a working hypothesis that several varieties of hyperphagia leading to obesity have a common element. This common factor is a change in excitability of a lateral hypothalamic reinforcement system as manifested in self-stimulation at a stimulation-bound feeding site. Understanding this feeding reward-aversion system helps us understand hyperphagia and anorexia. The neurochemistry of reward and aversion involves the monoamines. This paper focuses on dopamine and serotonin. The data support the hypothesis that dopamine systems projecting to the nucleus accumbens and other forebrain areas from the mid-brain ventral tegmental area (VTA) are important for approach and positive reinforcement in ingestive behavior and self-stimulation. Serotonin is hypothesized to facilitate satiety and inhibition of feeding reward in the hypothalamus. The next section abstracts our recent experiments that measured pharmacological and physiological release of the monoamines in the hypothalamus and nucleus accumbens during ingestive behavior and self-stimulation. In vivo microdialysis in freely moving rats suggested the following: (1) Norepinephrine was released in the paraventricular nucleus during the active, feeding period of the circadian cycle. (2) The serotonin metabolite 5-HIAA also increased in the PVN at the same time if there was food to eat. (3) Amphetamine infused into the lateral hypothalamus (LH) by reverse dialysis increased synaptic dopamine, norepinephrine, and serotonin. (4) The anorectic drug d-fenfluramine increased synaptic serotonin in the LH and also increased the dopamine metabolite DOPAC, suggesting that serotonin and dopamine in the LH might contribute to fenfluramine-induced satiety. Local d-fenfluramine injection into the LH or local infusion by reverse dialysis again increased serotonin and decreased 5-HIAA and interfered with local dopamine metabolism as reflected in decreased DOPAC and HVA. (5) Tryptophan, a serotonin precursor, given systemically at an anorectic dose, increased extracellular serotonin in the LH, but this effect was only detectable in food-deprived rats. This was seemingly pH independent (between 5.8 and 8). The passage other cations through CFo is strictly suppressed (even at pH 8 and with 300 mM NaCl in the medium).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Psychology, Princeton University, New Jersey 08544-1010.
authors.forename: B G
authors.initials: BG
authors.lastname: Hoebel
authors.forename: L
authors.initials: L
authors.lastname: Hernandez
authors.forename: D H
authors.initials: DH
authors.lastname: Schwartz
authors.forename: G P
authors.initials: GP
authors.lastname: Mark
authors.forename: G A
authors.initials: GA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects*; D002032:Bulimia / Q000628:therapy; D004298:Dopamine / Q000493:pharmacokinetics* / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D001068:Feeding and Eating Disorders / Q000503:physiopathology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000493:pharmacokinetics / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000493:pharmacokinetics* / Q000502:physiology
chemical_list: D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine