CART peptide in the nucleus accumbens regulates psychostimulants: Correlations between psychostimulant and CART peptide effects.

In this study, we reexamined the effect of Cocaine-and-Amphetamine-Regulated-Transcript (CART) peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide.

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion.

Aims/hypothesis: Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart (-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice.

CART Peptides and Drugs of Abuse: A Review of Recent Progress.

Earlier studies suggesting an involvement of cocaine and amphetamine regulated transcript peptide (CARTp) in the actions of drugs of abuse are confirmed in the most recent publications. This seems especially true for the psychostimulants where CARTp in the nucleus accumbens inhibits or regulates the actions of these drugs; the regulation is lost after repeated drug use which may be an important mechanism in addiction. The other drugs, including nicotine, alcohol, opiates, and perhaps caffeine can affect CARTp or CART mRNA levels.

Cocaine-and-Amphetamine Regulated Transcript (CART) peptide attenuates dopamine- and cocaine-mediated locomotor activity in both male and female rats: lack of sex differences.

Cocaine-and-Amphetamine Regulated Transcript peptide (CART peptide) is known for having an inhibitory effect on dopamine (DA)- and cocaine-mediated actions and is postulated to be a homeostatic, regulatory factor in the nucleus accumbens (NAc). Some sex differences in cocaine-mediated locomotor activity (LMA) and in the expression and function of CART peptide have been reported. However, it is not known if the inhibitory effect of CART peptide on cocaine-mediated LMA is sexually dimorphic.

Affinity labeling of membrane receptors using tissue-penetrating radiations.

Photoaffinity labeling, a useful in vivo biochemical tool, is limited when applied in vivo because of the poor tissue penetration by ultraviolet (UV) photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp) at low doses (<50 cGy or Rad), specific and irreversible binding was found on striatal dopamine transporters with 3 photoaffinity ligands for dopamine transporters, to different extents.

The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this.

Region- and sex-specific changes in CART mRNA in rat hypothalamic nuclei induced by forced swim stress.

Cocaine and amphetamine regulated transcript (CART) mRNA and peptides are highly expressed in the paraventricular (PVN), dorsomedial (DMH) and arcuate (ARC) nuclei of the hypothalamus. It has been suggested that these nuclei regulate the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system activity, and feeding behavior. Our previous studies showed that forced swim stress augmented CART peptide expression significantly in whole hypothalamus of male rats.

Collegial ethics: supporting our colleagues.

The goal of collegial ethics is to actively support our colleagues and to develop the skills needed to do so. While collegial interactions are key for our careers, there is little or no training in this. Many of our actions and reactions with our colleagues are instinctive.

Collegial ethics: what, why and how.

Collegial ethics (CE) proposes that we support our colleagues whenever possible. It is more of a focus on the feelings of others rather than on our own. In spite of the importance of collegial interactions, CE is not usually taught.

Intraperitoneal Administration of CART 55-102 Inhibits Psychostimulant-Induced Locomotion.

CART (cocaine and amphetamine regulated transcript) peptide functions as both a neurotransmitter and a hormone and is found both in the central nervous system (CNS) and in the periphery. CART peptide in the nucleus accumbens (NAc) has been implicated in the regulation of cocaine-dopamine-mediated locomotion and self-administration, and amphetamine-mediated locomotion and behavior. However, there are no studies on the effect of systemic administration of CART peptide on cocaine and amphetamine-mediated locomotion.

Forced swim stress elicits region-specific changes in CART expression in the stress axis and stress regulatory brain areas.

CART mRNA and peptides are highly expressed in the anatomical structures composing the hypothalamo-pituitary-adrenal (HPA) axis and sympatho-adrenal system. Anatomical and functional studies suggest that CART peptides may have a role in the regulation of the neuroendocrine and autonomic responses during stress. Our previous study showed that CART peptides increased significantly in the male hypothalamus and amygdala 10min after the forced swim stress.

CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6-38 as a CART receptor antagonist.

CART peptides are peptide neurotransmitters and hormones that are involved in many different physiological responses. While much is known about the peptides regarding their structure, processing and gene regulation, less is known about their postsynaptic actions and receptors. Using (125)I-CART 61-102 as a ligand and unlabeled CART 61-102 or CART 55-102 as displacers, high-affinity specific binding was detected in PC12 cells.

Developing and communicating responsible data management policies to trainees and colleagues.

The basic components of data management including data ownership, collection, selection, recording, analysis, storage, retention, destruction, and sharing. A number of important principles underlie best practices for each of these components; these include recording details such that another can repeat the experiment, keeping the data safe, managing storage in such a way as to facilitate easy retrieval for the period of time required by regulatory agencies and establishing data sharing principles with colleagues before collaborations begin. Experience as practicing scientists and teachers has aided in developing helpful strategies and approaches for communicating these principles, policies and practices to trainees and colleagues.

CART peptide inhibits locomotor activity induced by simultaneous stimulation of D1 and D2 receptors, but not by stimulation of individual dopamine receptors.

CART (Cocaine- and amphetamine-regulated transcript) peptide has been implicated in playing a modulatory role in reward and reinforcement. Previously, our laboratory demonstrated that injections of CART peptide (CART 55-102) into the nucleus accumbens (NAc) attenuated both cocaine- and dopamine-induced increases in locomotor activity (LMA), and attenuated cocaine reward as well. In this study, the effects of CART peptide on LMA induced by dopamine receptor agonists were evaluated after intraaccumbal injections in male, Sprague-Dawley rats.

Chromatin immunoprecipitation assays revealed CREB and serine 133 phospho-CREB binding to the CART gene proximal promoter.

Both over expression of cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc), and intra-accumbal injection of cocaine- and amphetamine-regulated transcript (CART) peptides, have been shown to decrease cocaine reward. Also, over expression of CREB in the rat NAc increased CART mRNA and peptide levels, but it is not known if this was due to a direct action of P-CREB on the CART gene promoter. The goal of this study was to test if CREB and P-CREB bound directly to the CRE site in the CART promoter, using chromatin immunoprecipitation (ChIP) assays.

Wake promoting effects of cocaine and amphetamine-regulated transcript (CART).

Cocaine- and amphetamine-regulated transcript (CART) peptides modulate anxiety, food intake, endocrine function, and mesolimbic dopamine related reward and reinforcement. Each of these disparate behaviors takes place during the state of wakefulness. Here, we identify a potential wake promoting role of CART by characterizing its effects upon sleep/wake architecture in rats.

Measuring levels of proteins by various technologies: can we learn more by measuring turnover?

In routine experiments, scientists measure the levels of various substances such as proteins after various treatments. Detection of a change in levels suggests an impact of treatment on that particular protein. However, we sometimes forget the importance of turnover in this process.

Regulation of CART peptide expression by CREB in the rat nucleus accumbens in vivo.

Production of mRNA from the cocaine- and amphetamine-regulated transcript (CART) gene is regulated by cocaine and other drugs of abuse in the nucleus accumbens (NAc), a brain reward region. Current hypotheses postulate that CART peptides there oppose the rewarding actions of cocaine by opposing the effects of dopaminergic transmission. Since over expression of CREB was shown to decrease cocaine-mediated reward, we hypothesized that CART could be a target gene for CREB in the NAc and that over expression of CREB would increase CART peptide levels.