Individual differences in cocaine-induced conditioned place preference in male rats: Behavioral and transcriptomic evidence.

BACKGROUND: Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology. AIMS: Our study aimed to demonstrate and characterize the variability in the expression of the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. METHODS: A cocaine-CPP paradigm in male Sprague-Dawley rats with an extinction period of 12 days and reinstatement was conducted. A statistical model was developed to distinguish rats expressing or not a cocaine-induced place preference. RESULTS: Two groups of rats were identified: rats that did express rewarding effects (CPP expression (CPPE), score >102 s) and rats that did not (no CPP expression (nCPPE), score between -85 and 59 s). These two groups did not show significant differences in a battery of behavioral tests. To identify differentially expressed genes in the CPPE and nCPPE groups, a whole-transcriptome ribonucleic acid-sequencing analysis was performed in the nucleus accumbens (NAc) 24 h after the CPP test. Four immediate early genes (Fos, Egr2, Nr4a1, and Zbtb37) were differentially expressed in the NAc of CPPE rats after expression of CPP. Variability in cocaine-induced place preference persisted in the CPPE and nCPPE groups after the extinction and reinstatement phases. Transcriptomic differences observed after reinstatement were distinct from those observed immediately after expression of CPP. CONCLUSION: These new findings provide insights into the identification of mechanisms underlying interindividual variability in the response to cocaine's rewarding effects.

Giant Shape-Persistent Tetrahedral Porphyrin System: Light-Induced Charge Separation.

Tetraphenylmethane appended with four pyridylpyridinium units works as a scaffold to self-assemble four ruthenium porphyrins in a tetrahedral shape-persistent giant architecture. The resulting supramolecular structure has been characterised in the solid state by X-ray single crystal analysis and in solution by various techniques. Multinuclear NMR spectroscopy confirms the 1 : 4 stoichiometry with the formation of a highly symmetric structure. The self-assembly process can be monitored by changes of the redox potentials, as well as by modifications in the visible absorption spectrum of the ruthenium porphyrin and by a complete quenching of both the bright fluorescence of the tetracationic scaffold and the weak phosphorescence of the ruthenium porphyrin. An ultrafast photoinduced electron transfer is responsible for this quenching process. The lifetime of the resulting charge separated state (800 ps) is about four times longer in the giant supramolecular structure compared to the model 1 : 1 complex formed by the ruthenium porphyrin and a single pyridylpyridinium unit. Electron delocalization over the tetrameric pyridinium structure is likely to be responsible for this effect.

Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat.

BACKGROUND: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability. AIMS: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties. METHODS: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex. RESULTS: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex. CONCLUSIONS: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.

Photoinduced hydrogen evolution by a pentapyridine cobalt complex: elucidating some mechanistic aspects.

A new hydrogen evolving cobalt catalyst 1 based on a pentapyridine ligand has been synthesized and characterized. Its photocatalytic activity in the presence of a Ru(bpy)3(2+) sensitizer and ascorbic acid as a sacrificial electron donor has been screened in purely buffered aqueous solutions showing TONs and TOFs strongly dependent on both catalyst concentration and pH with the best results obtained at 50 µM 1 and at pH 4 (TON = 187, TOF = 8.1 min(-1)). The photochemical mechanism, as revealed by flash photolysis, involves reaction of the excited sensitizer with ascorbic acid to yield Ru(bpy)3(+) as a primary photo-generated reductant, capable of electron transfer to 1 with a remarkable rate (bimolecular rate constant k = 5.7 (±0.7) × 10(9) M(-1) s(-1)). For hydrogen generation, two one-electron photochemical reduction steps of 1 are needed along with hydride formation and protonation. Under the experimental conditions used, hydrogen evolution is mainly limited by partial decomposition of both the sensitizer and the catalyst. Moreover, accumulation of the oxidation product of the ascorbic acid donor, dehydroascorbic acid, is observed to strongly decrease the hydrogen production yield. As shown by flash photolysis, this species is capable of quenching the reduced ruthenium species (k = 4.4 (±0.5) × 10(7) M(-1) s(-1)) thus competing with electron transfer to the catalyst.

Efficient photocatalytic hydrogen generation from water by a cationic cobalt(II) porphyrin.

Efficient photocatalytic hydrogen evolution is obtained from 1 M phosphate buffer at pH 7 in the presence of a Ru(bpy)3(2+) sensitizer, an ascorbic acid sacrificial donor, and a water-soluble Co(II) porphyrin catalyst. Spectroscopic investigation of the system by stationary and time-resolved techniques enables a complete characterization of the photoinduced dynamics.