CART peptide and the mesolimbic dopamine system.

Over the past decade, CART peptide has been commonly associated with the rewarding and reinforcing properties of drugs of abuse and natural rewards such as food. The mesolimbic dopamine system is the predominant pathway involved in mediating reward and reinforcement. Many behavioral and neuroanatomical studies have been conducted in order to further elucidate the importance of CART-containing neurons within the mesolimbic dopamine system.

Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial.

750 mg per day of acetazolamide in the prevention of acute mountain sickness (AMS), as recommended in the meta-analysis published in 2000 in the British Medical Journal, may be excessive and is controversial. To determine if the efficacy of low-dose acetazolamide 125 mg bd (250 mg), as currently used in the Himalayas, is significantly different from 375 mg bd (750 mg) of acetazolamide in the prevention of AMS, we designed a prospective, double-blind, randomized, placebo-controlled trial. The participants were sampled from a diverse population of (non-Nepali) trekkers at Namche Bazaar (3440 m) in Nepal on the Everest trekking route as they ascended to study midpoints (4280 m/4358 m) and the endpoint, Lobuje (4928 m), where data were collected.

Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets.

Cocaine- and amphetamine-regulated transcript (CART) peptides (55 to 102 and 62 to 102) are neurotransmitters with important roles in a number of physiologic processes. They have a role in drug abuse by virtue of the fact that they are modulators of mesolimbic function. Key findings supporting a role in drug abuse are as follows.

Species differences in brain distribution of CART mRNA and CART peptide between prairie and meadow voles.

Reward mechanisms are involved in pair bond formation in monogamous prairie voles. Given the potential role of CART (cocaine- and amphetamine-regulated transcript) in reward, and its possible role as a third neurohypophysial hormone, we examined the brain distribution of CART mRNA and peptide in monogamous prairie voles compared to congener promiscuous meadow voles. Large species differences in CART mRNA distribution were apparent in the nucleus accumbens, bed nucleus of the stria terminalis, hippocampus, and cortex.

CART peptide diurnal rhythm in brain and effect of fasting.

We have recently shown that CART peptides exhibit a diurnal rhythm in blood that is affected by food intake and glucocorticoids. In the present study, we extend our observations by demonstrating that CART peptides also exhibit a diurnal rhythm in several brain regions, notably the nucleus accumbens, hypothalamus and amygdala, but not in the midbrain. To examine whether the CART peptide rhythm was dependent on food intake, animals were food-deprived for 24 h.

CART in feeding and obesity.

CART (cocaine- and amphetamine-regulated transcript) peptides are neurotransmitters that have received much attention as mediators of feeding behavior and body-weight regulation in mammals. CART peptides and their mRNAs are found in many brain regions and in peripheral tissues that are involved in feeding, and many animal studies implicate CART as an inhibitor of feeding. Animal studies also demonstrate that CART expression is regulated by both leptin and glucocorticoids, two hormones known to be associated with the regulation of body weight.

Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity.

Evidence suggests that CART (cocaine-amphetamine regulated transcript) peptides are mediators or modulators of the actions of psychostimulant drugs. In this study, the effects of intra-accumbal injections of rat long form (rl) CART 55-102 were examined. Injection of the peptide alone had no effect, but pretreatment with the peptide blunted or reduced the locomotor-inducing effects of cocaine after an i.