Oral contraceptive effects on food choice during the follicular and luteal phases of the menstrual cycle. A laboratory based study.

Fifty-five women were recruited and assigned to a control group or an oral contraceptive (OC) use group. For the control groups menstrual cycle phase was determined using a menstrual calendar and only participants with regular cycles were recruited. Testing was carried out during a single day of the luteal and follicular phases, where participants were asked to consume and rate sweet and savoury snacks. Participants in the OC group were tested on the equivalent days of their pill calendar. In both groups, the luteal phase induced a greater caloric intake of sweet foods without altering hedonic ratings. No significant interactions between either phase or flavour with OC use on food intake or hedonic food ratings were found. At least for snack items, OC do not seem to alter the caloric intake fluctuations that occur during a normal menstrual cycle.

Therapeutic potential of targeting the endocannabinoids: implications for the treatment of obesity, metabolic syndrome, drug abuse and smoking cessation.

Rimonabant (SR141716, Acomplia) has been described as an antagonist/inverse agonist at the cannabinoid receptor type 1 (CB1). It has been widely used as a tool to evaluate the mechanisms by which cannabinoid agonists produce their pharmacological effects and to elucidate the respective physiological or pathophysiological roles of the CB1 receptor. It has become increasingly clear that rimonabant can exert its own intrinsic actions. These may be viewed as evidence of either the inverse agonist nature of rimonabant or of tonic activity of the endocannabinoid system. To date, data obtained from clinical trials (RIO North America, RIO Europe and RIO Lipid) indicate that rimonabant may have clinical benefits in relation to its anti-obesity properties and as a novel candidate for the treatment of metabolic and cardiovascular disorders associated with overweight and obesity. Other clinical trials, such as the STRATUS study, have also shown that rimonabant may be effective in smoking cessation, and that the drug has a reasonable safety profile. Recently, it has been shown that rimonabant prevents indomethacin-induced intestinal injury by decreasing the levels of pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha), thus indicating that CB1 receptor antagonists might exhibit potential anti-inflammatory activity in acute and chronic diseases.

Endocannabinoids in appetite control and the treatment of obesity.

Research into the endocannabinoid 'system' has grown exponentially in recent years, with the discovery of cannabinoid receptors and their endogenous ligands, such as anandamide and 2-arachidonoylglycerol (2-AG). Important advances have been made in our understanding of endocannabinoid transduction mechanisms, their metabolic pathways, and of the biological processes in which they are implicated. A decade of endocannabinoid studies has promoted new insights into neural regulation and mammalian physiology that are as revolutionary as those arising from the discovery of the endogenous opioid peptides in the 1970s. Thus, endocannabinoids have been found to act as retrograde signals: released by postsynaptic neurons, they bind to presynaptic heteroceptors to modulate the release of inhibitory and excitatory neurotransmitters through multiple G-protein-coupled receptor (GPCR)-linked effector mechanisms. The metabolic pathways of anandamide and 2-AG have now been been characterised in great detail, and we can anticipate that these pathways -- together with endocannabinoid uptake mechanisms -- will complement cannabinoid receptors as targets for the pharmacological analysis of the physiological functions of these substances. Specific insights into the potential role of endocannabinoid-CB1 receptor systems in central appetite control, peripheral metabolism and body weight regulation herald the clinical application of CB1 receptor antagonists in the management of obesity and its associated disorders.

Methyllycaconitine (MLA) blocks the nicotine evoked anxiogenic effect and 5-HT release in the dorsal hippocampus: possible role of alpha7 receptors.

Nicotine has bimodal effects on anxiety, with low doses having an anxiolytic effect and high doses having an anxiogenic effect. The dorsal hippocampus is one of the brain areas that mediate the anxiogenic effect of nicotine through enhanced 5-HT release, but the nAChR subtype(s) that mediate these effects are not known. Intrahippocampal administration of a high dose of nicotine (1 micro g, 4.3 mM) had an anxiogenic effect in the social interaction test that was reversed by co-administration of a behaviourally inactive dose (1.9 ng, 4.3 micro M) of methyllycaconitine (MLA), which is an antagonist at alpha7 and alpha3 nAChR subunits. At a dose (0.8 ng, 4.3 micro ;M) at which its actions would be specific to alpha4beta2 and alpha3beta2 nAChRs dihydro-beta-erythroidine (DHbetaE) was unable to reverse nicotine's anxiogenic effect. Reversal was obtained with a 10-fold higher, but receptor non-specific concentration of DHbetaE (7.8ng, 43 micro M), suggesting that the DHbetaE reversal might have been due to action at alpha7 nAChRs. Exposure of hippocampal slices to MLA (0.25, 05, 1 and 10 micro M) significantly reduced the increase in [(3)H]5-HT release evoked by nicotine (100 micro M). DHbetaE (0.1-0.5 micro M) failed to reverse this effect of nicotine on [(3)H]5-HT release, although higher concentrations (1 and 10 micro M), at which alpha7 subunits would also be affected, were able to do so. Because of the lack of effects of low, receptor specific concentrations of DHbetaE, it is more likely that the MLA reversal of both nicotine's anxiogenic effect and its stimulation of [(3)H]5-HT release is due to action at alpha7 than at alpha3 units. This is perhaps also more likely because the alpha7 receptors are highly expressed in the dorsal hippocampus, whereas the alpha3 subunits are much less abundant. However, what is most important is that, in the dorsal hippocampus, nicotine's anxiogenic effect and induced release of [(3)H]5-HT are mediated by non alpha4beta2 nAChRs, which contrasts with the previously reported anxiolytic effect of a low dose of nicotine which is mediated by alpha4beta2 nAChRs within the dorsal raphé nucleus. Thus the anxiolytic and anxiogenic effects of nicotine can be distinguished both by brain region and by nicotinic receptor subtype.