Interazioni neurotrasmettitoriali nel meccanismo d’azione della cocaina: ruolo della serotonina e dell’adenosina

The putative 5-HT6 receptor agonist ST1936 has been shown to increase extracellular dopamine (DA) in the n.accumbens (NAc) Shell and in the medial prefrontal cortex (PFCX). These observations suggest that 5-HT6 receptors modulate DA transmission in mesolimbic and mesocortical terminal DA areas. To investigate the behavioral counterpart of this interaction I studied in rats the effect of 5-HT6 receptor blockade on cocaine stimulated overflow of DA in dialysates from the PFCX and from the NAc Shell and on cocaine i.v. selfadministration. Pretreatment with the 5-HT6 antagonist SB271046 reduced cocaine-induced increase of dialysate DA in the NAc Shell but not in the PFCX and impaired i.v. cocaine selfadministration. These suggest that 5-HT6 receptors play a role in cocaine reinforcement via their facilitatore interaction with DA projections to the NAc Shell. This 5-HT/DA interaction might provide the basis for a new pharmacotherapeutic strategy of cocaine addiction. Caffeine is one of the psychoactive substances most widely used as adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. In the present study I examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using the intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. To this end, we assessed in naïve rats: 1) the ability of the combination of cocaine (0,125 mg/kg/infusion) and caffeine (0,0625 mg/kg/infusion) to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine and caffeine alone; 2) the effect of caffeine in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. Cocaine and the combination of cocaine and caffeine were self-administered on a FR and PR schedules of reinforcement, and the responding for the combination of the drugs was higher than cocaine alone. Caffeine was not reliably self-administered, but was able to maintain a drug-seeking behavior in rats previously exposed to cocaine plus caffeine. These findings suggest that the presence of caffeine enhances the reinforcing effects of cocaine and the motivational value of the drug. Our results highlight the role of active adulterants commonly used in illicit street drugs.

Ruolo e limiti del contratto negli assetti familiari in funzione successoria

The Article 457 c.c. expressly excludes the contract by the sources of the succession. Moreover, the article 458 c.c., apart from the initial brief aside dedicated to the institute of the family pact, agrees nullity of the agreements with whom someone decides its own succession as well as those with which the future successor could decide about his rights or renounce to them about a succession not yet open. However, for a long time, the Italian doctrine wonders about the role of the contract within the succession law. It feels, in fact, the need to expand the private autonomy within the inheritance that is excessively sacrificed by the prohibition of succession agreements and by the norms for the protection of legitimate heirs. The reasons which led the legal science to these conclusions are based on different events, both social and economic, that push the interpreter to a modernization of dogmatic categories with which he can represent the succession mortis causa. In addiction, it is necessary to underline the crisis of the agreements mortis causa due to this economical and social events: as a matter of fact, the will, as the only way to give the assets post mortem, revealed itself incomplete and extremely severe compared to the new social needs. In fact, increasingly the way to give the assets happens out of the inheritance and despite to the institutions designed by the law. For these reasons, in order to adapt the system of succession to modern economic and social needs, the doctrine has identified, within the system, institutions of a contractual nature in order to better achieve the interests of private, obviating the limits assigned to the shop last will. And recently, in this context, our legislator has introduced the institution of the family pact (art. 768 bis et seq. c.c.), that is the agreement through “the entrepreneur transfers, in whole or in part , the company, and the holder of equity investments transfers, in whole or in part, its shares, to one or more descendants". While, however, part of the doctrine encourages the provision of tools that enable a person to have in advance of his succession, on the other hand there are those who promote the centrality of the will within our legal system and calls for the revitalization in respect of its vast potential is not always adequately exploited. This research aims to verify whether the contract can find importance within the phenomenon of succession for the inter vivos transfer of family assets and if the same has the characteristics to be considered a working alternative to the will. In the present work will be analyzed, in addition, some of the institutions that the doctrine has considered alternatives to the will and particularly the institution of the family pact. The survey will also be directed to the limits that the private autonomy and the legislator met in the use of the contractual instrument, limits that are mostly originated by the rules and principles of the law of succession.