Microdialysis Studies of Brain Norepinephrine, Serotonin, and Dopamine Release During Ingestive Behavior Theoretical and Clinical Implicationsa

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)

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…There is high comorbidity between BN and substance abuse, and there is a considerable body of data suggesting that disturbed appetitive behaviors for food in BN may reflect a dysregulation of reward mechanisms that is common to both BN and substance-abuse disorders [317]. Indeed, early hallmark preclinical studies by Hoebel and colleagues [318] highlighted commonalities between BN and addiction disorders in terms of neurobiology, psychopharmacology, neurochemistry, and behavior [319]. Binge eating has also been suggested to serve an emotion regulatory function, and thus has many qualities of reward-mediated behaviors [320].…”

Accumbens dopamine-acetylcholine balance in approach and avoidance

“…Early microdialysis studies found that instrumental feeding responses or appetitive hypothalamic stimulation releases DA in the NAc, and it can stay high for some time afterward [16]. DA release can carry information as to sucrose concentration and thus palatability [17].…”

Food reinforcement and eating: A multilevel analysis.

“…It is possible that conditioned increases in dopaminergic activity that are elicited by stimuli associated with eating play a role in craving for food (Berridge, 1996). Initially, dopamine is released when food is consumed (Hoebel, Hernandez, Schwartz, Mark, & Hunter, 1989), and its activity in the nucleus accumbens may relate not only to consumption but also to rewarding properties of food (Hernandez & Hoebel, 1988). Over repeated pairings of an environmental stimulus with eating, dopamine is released after presentation of a cue paired with food in anticipation of eating.…”