Appetite, serotonin

Boadle-Biber, MC (1993) Regulation of serotonin S5mthesis. Prog. Biophys. Molec. Biol. 60 1-15. Curzon, G, Gibson, EL and Oluyomi, AO (1997) Appetite suppression by commonly used drugs depends on 5-HT receptors but not on 5-HT availability. Trends Pharmacol. Sci. 18 21-25. Gaddum, JH and Picarelli, ZP (1957) Two kinds of tr5 ptamine receptor. Brit. J. Pharmacol. 12 323-328. (Reproduced in Brit. J. Pharmacol. 120 (Suppl) 134-139.)... 

Rats that have lost dopamine and/or serotonin terminals following treatment with amphetamine, methamphetamine, MDMA, MDA, / -chloroamphetamine, or fenfluramine show little in the way of overt ehanges in appearanee or behavior. Dr. Rieaurte (this volume) emphasized the need for more studies in primates, since MPTP-treated miee also show little in the way of observable functional changes, whereas MPTP-treated monkeys show marked neurologie deficits. It may be neeessary to do more detailed analysis of speeifie behaviors and other funetional outputs that are influeneed by dopamine and/or serotonin neurons, to detect functional deficits induced by some neurotoxic drugs. For instance, specific behaviors sueh as appetite-eontrolled behavior (Leibowitz and Shor-Posner 1986), murieidal behavior (Katz 1980), and sexual behavior (Tucker and File 1983) elieited by drugs... 

Leibowitz, S.F., and Shor-Posner, G. Brain serotonin and eating behavior. Appetite 7 [Suppl] l-14, 1986. 

Sibutramine and its two active metabolites (Mj and M2) exert their effect by inhibiting the reuptake of serotonin, norepinephrine, and dopamine.29 Appetite becomes suppressed because patients feel a sense of satiety. 

Dopamine, norepinephrine, and serotonin have other responsibilities in the body besides dictating hunger. For example, norepinephrine also helps control blood pressure. Drugs that affect the level of these neurotransmitters interfere with other body processes and produce negative side effects. A drug that increases norepinephrine will decrease appetite, but... 

Figure 3.2 Normally, when the stomach is full it sends a signal to the brain telling the body to stop eating. This message is carried by neurotransmitters (chemical messengers in the brain) to the hunger center in the hypothalamus (a part of the brain). Examples of neurotransmitters that carry this message are norepinephrine, serotonin, and dopamine. Many diet pills increase these same neurotransmitters that signal the brain that the stomach is full. These diet pills, called appetite suppressants, trick the brain into thinking the stomach is full and therefore decrease hunger.

HT may be involved in a wide variety of behaviors by setting the tone of brain activity in relationship to the state of behavioral arousal/activity. Serotonin has been implicated in practically every type of behavior, e.g. appetitive, emotional, motoric, cognitive, autonomic. However, from a physiologic perspective, it is not clear whether 5-HT affects such behaviors specifically, or more generally by coordinating the activity of the nervous system, particularly to set the tone of activity in conjunction with the organism s level of arousal. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Many commonly used medications also contain substances that are eliminated by the MAOIs and must not be taken by these patients. The list of medications to be avoided inclndes the narcotic pain reliever meperidine (Demerol), and many over-the-connter cold remedies containing dextromethorphan or pseudoephedrine. Finally, patients taking MAOIs must also avoid medications that elevate serotonin levels. This inclndes certain appetite snppressants and antidepressants including the SSRIs, venlafaxine, duloxetine, mirtazapine, nefazodone, and trazodone. Medications that interact with the MAOIs cannot be taken until at least 2 weeks after the MAOI has been stopped. 

When starting a SSRI, the abrupt increase in serotonin may cause side effects. In the brain, the short-term effects include headache, sleep disturbance, nervousness, anxiety, and tremulousness. The digestive system effects include nausea, loose stools, decreased appetite, and indigestion. Most of these effects are mild and shortlived or can be managed with over-the-counter remedies. Nausea, for example, can be minimized by taking a SSRI after meals. These effects are also commonly seen with venlafaxine and duloxetine, atypical antidepressants that block serotonin reuptake like the SSRIs. 

Appetite Stimulants. A large body of neuroscience research indicates that serotonin plays a prominent role in the modulation of appetite. Increases in serotonin availability in certain brain regions confer a sense of satiety, and decreases of serotonin are associated with hunger. Consequently, agents that block the release or action of serotonin in the brain increase appetite and should theoretically be helpful in the treatment of AN. 

Cyproheptadine (Periactin). Cyproheptadine is an antihistamine, commonly used to alleviate allergy symptoms, that also has serotonin-blocking properties. It has been successfully used to stimulate appetite in patients with medical illnesses such as cancer or AIDS. Cyproheptadine provides a small but measurable benefit in the rapidity of weight gain during the refeeding of patients with the restricting subtype of AN. However, bulimic subtype patients apparently fare worse with the addition of cyproheptadine. 

The newest appetite suppressant, sibutramine (Meridia), works by blocking the reuptake of both serotonin and norepinephrine. It does not stimulate nerve cells to release serotonin, as do fenfluramine and dexfenfluramine. Administered at 20 mg/ day, sibutramine effectively reduces weight in obese patients, but its use has not been assessed in eating disorder patients. The most common side effects of this medication are insomnia, dry mouth, and constipation. It has not been associated with the more serious heart and lung complications observed with fenfluramine and dexfenfluramine. Because sibutramine acts in part through modulation of norepinephrine, there is no rational basis for coadministering phentermine, which acts via this same mechanism. 

Sibutramine is a centrally acting appetite suppressant used as an adjunct in the management of obesity. It inhibits the re-uptake of noradrenaline and serotonin. 

The 5-HTja receptor was first described in 1981 and is perhaps the best characterized of the serotonin receptors. 5-HTja receptors have been implicated in the regulation of aggression, affect, anxiety, appetite, sexual behavior, and in the control of stress-related disorders [Dourish et al. 1987]. Also, these receptors play a major role in modulating serotonergic transmission. 

Kumar KB, Nalini K, Karanth KS Effects of p-chlorophenylalamine induced depletion of brain serotonin on retrieval of appetitive and aversive memories. Indian J Exp Biol 33 837-840, 1995... 

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