5-hydroxytryptamine medications for the treatment of obesity.

The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.

Melanocortin-3 receptors are involved in adaptation to restricted feeding.

The central nervous melanocortin system forms a neural network that maintains energy homeostasis. Actions involving neural melanocortin-3 receptors (MC3Rs) regulate the expression rhythms in ingestive behaviors and metabolism anticipating nutrient intake. Here, we characterized the response of Mc3r knockout (Mc3r(-/-)) and wild type (WT) mice to a restricted feeding (RF) schedule where food access was limited to a 4-h period mid light cycle using a mechanical barrier. Mc3r(-/-) mice adapted poorly to the food restriction schedule. Anticipatory activity and the initial bout of intense feeding activity associated with granting food access were attenuated in Mc3r(-/-) mice, resulting in increased weight loss relative to controls. To investigate whether activity in specific hypothalamic nuclei contribute to the Mc3r(-/-) phenotype observed, we assessed hypothalamic FOS-immunoreactivity (FOS-IR) associated with food restriction. Food access markedly increased FOS-IR in the dorsomedial hypothalamus (DMH), but not in the suprachiasmatic or ventromedial hypothalamic nuclei (SCN and VMN, respectively) compared to ad libitum fed mice. Mc3r(-/-) mice displayed a significant reduction in FOS-IR in the DMH during feeding. Analysis of MC3R signaling in vitro indicated dose-dependent stimulation of the extracellular signal-regulated kinase (ERK) pathway by the MC3R agonist d-Trp(8)-γMSH. Treatment of WT mice with d-Trp(8)-γMSH administered intracerebroventricularly increased the number of pERK neurons 1.7-fold in the DMH. These observations provide further support for the involvement of the MC3Rs in regulating adaptation to food restriction. Moreover, MC3Rs may modulate the activity of neurons in the DMH, a region previously linked to the expression of the anticipatory response to RF.

Food images engage subliminal motivation to seek food.

Human eating behaviour is motivated and shaped by a complex interaction of internal drives such as hunger, external influences such as environmental cues and the sensory properties of food itself. Thus, as is demonstrated by the example of sensory-specific satiety (SSS), hunger may be reduced but particular foods (for example, desserts) retain their attraction and their ability to prompt consumption. In considering consumption, and overconsumption, it is therefore important to understand the interaction between internal and external drives to eat. Using grip force as a measure of motivation, we examined this interaction using an SSS manipulation. Critically, we sought to determine whether food stimuli would exert their influence even when they were subliminally presented (and thus not accessible to consciousness), and whether this unconscious influence would be flexibly updated in response to changes in food reward value with satiety. Demonstrating that the SSS effect remains when external stimuli are not consciously perceived, our data highlight the importance of even the most subtle, fleeting and even subliminal external events in shaping our motivation towards food.

Violence in lesbian and gay relationships: theory, prevalence, and correlational factors.

This article reviews and critiques the existing empirical literature examining interpersonal violence in lesbian and gay relationships. Studies assessing psychological, physical, and nonconsenting sexual forms of violence in intimate, same-sex relationships are reviewed, and their findings are integrated with what is known about partner abuse in heterosexual relationships. Nineteen studies are described and categorized according to the specific questions being addressed. This body of literature suggests that prevalence rates of same-sex partner abuse are high and its correlates show many similarities to those identified in incidents of heterosexual partner abuse. This article addresses the need for substantially increased efforts in this field of study in terms of well-controlled and theory-driven research design. In terms of other implications of this body of literature, the high prevalence rate of partner abuse among lesbian and gay populations needs to be recognized by providers of both physical and mental health services who potentially treat victims, so that they can more accurately identify appropriate interventions. More research is warranted, not only in the general area of lesbian and gay partner abuse, but in examining various treatment modalities and their effectiveness in helping perpetrators to end the cycle of violence.