Dopaminergic, glutamatergic but not opioidergic mechanisms mediate induction of FOS-like protein by cocaethylene

Cocaethylene is a psychoactive metabolite formed\ud during the combined consumption of cocaine and ethanol. As\ud this metabolite has many properties in common with cocaine, it is conceivable that cocaethylene administration may induce the activity of nuclear transcription factors that regulate the expression of late-response genes. Therefore, the temporal induction of FOS-like protein in rat brain was examined following IP administration of 60 mmol/kg cocaethylene. Immunoreactivity for the protein was detectable at 1 h in striatal neurons and had virtually disappeared 6 h after drug treatment. Administration of\ud specific dopaminergic (SCH-23390; 0.5 mg/kg) and glutamatergic (MK-801; 1 mg/kg) receptor antagonists prior to cocaethylene indicated a significant role for dopamine (D1) and Nmethyl-D-aspartate receptor subtypes in mediating the nuclear induction of the aforementioned transcription factor protein. In contrast, no significant effects on FOS-like protein in discrete neurons of the caudate putamen were found when spiradoline (U-62066), a kappa opioid-receptor agonist, was administered either IP (10 mg/kg) or directly (50 nmol) into the brain parenchyma. In addition, we uncovered a differential sensitivity of Long–Evans rats to the behavioral effects of cocaethylene, with the psychoactive metabolite producing significantly less behavioral activity (e.g., locomotion, rearing, and continuous sniffing)than that produced by cocaine (molar equivalent of 60 mmol/kg cocaethylene). These findings indicate both common and disparate effects of cocaethylene and its parent compound, cocaine, on receptor pathways that regulate target alterations in gene expression and drug-induced motor behavior

Differential Behavioral Responses to\ud Cocaethylene of Long-Evans and\ud Sprague-Dawley Rats: Role of Serotonin

Cocaethylene is a neuroactive metabolite derived from the concurrent consumption of cocaine and ethanol. The effects of cocaethylene on locomotor activity, stereotypy, and rearing in Long-Evans and Sprague-Dawley rats were compared.A single cocaine injection (molar equivalent of 60 μmol/kg cocaethylene, intraperitoneal) elicited a robust series of motor output behaviors, including locomotion, stereotypy, and rearing over a 30-minute testing period in Long-Evans rats. In contrast, cocaethylene administration,\ud under comparable testing conditions, produced no significant changes in locomotor and investigatory behaviors. Because cocaethylene has relatively little impact on serotonin (5-HT) reuptake as opposed to reuptake of dopamine, we pretreated Long-Evans rats with fluoxetine (10 mg/kg; IP), a selective 5-HT reuptake inhibitor. Fluoxetine profoundly augmented cocaethylene-stimulated behaviors in this rat phenotype. To examine whether other rat strains exhibit a similar response to cocaethylene, Sprague-Dawley rats were injected (IP) with cocaethylene and their behavior patterns monitored over a 30-minute testing period. Cocaethylene produced marked locomotor and exploratory behaviors in this strain, suggesting therefore that Long-Evans and Sprague-\ud Dawley rats differ in their response to cocaethylene. To relate these behavioral differences to possible structural differences in the neuronal density of dopaminergic or\ud serotonergic neurons, Long-Evans and Sprague-Dawley brains were evaluated for tyrosine hydroxylase and 5-HT immunocytochemistry. No gross morphological differences\ud in neuronal architecture or density were found in the ventral tegmental area or dorsal raphe nucleus of the two rat phenotypes. These results indicate that two commonly used rat strains show a differential response to cocaethylene and the neurochemical basis for this behavioral difference may be related to synaptic 5-HT bioavailability

Effects of cocaethylene on dopamine and serotonin synthesis in Long–Evans and Sprague–Dawley brains

We examined the behavioral and neurochemical effects of cocaethylene treatment in Long–Evans (�LE). and Sprague–Dawley� (SD) rats. Cocaethylene-induced behaviors were significantly less in LE rats. Cocaethylene caused an inhibition of dopamine synthesis in the caudate nucleus and nucleus accumbens that was equivalent in both rat lines. Serotonin synthesis was also suppressed by cocaethylene treatment, however this phenomenon was less pronounced when compared with the effects on dopamine synthesis

Nuclear Equation of state for Compact Stars and Supernovae

International audienceThe equation of state (EoS) of hot and dense matter is a fundamental input to describe static and dynamical properties of neutron stars, core-collapse supernovae and binary compact-star mergers. We review the current status of the EoS for compact objects, that have been studied with both ab-initio many-body approaches and phenomenological models. We limit ourselves to the description of EoSs with purely nucleonic degrees of freedom, disregarding the appearance of strange baryonic matter and/or quark matter. We compare the theoretical predictions with different data coming from both nuclear physics experiments and astrophysical observations. Combining the complementary information thus obtained greatly enriches our insights into the dense nuclear matter properties. Current challenges in the description of the EoS are also discussed, mainly focusing on the model dependence of the constraints extracted from either experimental or observational data (specifically, concerning the symmetry energy), the lack of a consistent and rigorous many-body treatment at zero and finite temperature of the matter encountered in compact stars (e.g. problem of cluster formation and extension of the EoS to very high temperatures), the role of nucleonic three-body forces, and the dependence of the direct URCA processes on the EoS