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.

Una testimonianza silenziosa.Storia della Chiesa cattolica in Tunisia dal Trattato del Bardo alla ‘rivoluzione dei gelsomini’

The work examines the change involving the Church in Tunisia from the period of the Protectorate to the present through the fundamental moments of independence (1956) and the signing of the ‘Modus vivendi’ (1964). In the first structure of the “modern” Church, a fundamental role was played by the complex figure of the French Cardinal Charles-Allemand Lavigerie who, while giving strong impulse to setting up disinterested charitable social initiatives by the congregations (Pères Blancs, Soeurs Blanches and others), also represented the ideal of the ‘evangelizing’ (as well as colonial) Church which, despite its declared will to avoid proselytism, almost inevitably tended to slip into it. During the French Protectorate (1881-1956) the ecclesiastic institution concentrated strongly on itself, with little heed for the sensitivity of its host population, and developed its activities as if it were in a European country. From the social standpoint, the Church was mostly involved in teaching, which followed the French model, and health facilities. In the Church only the Pères Blancs missionaries were sincerely committed to promoting awareness of the local context and dialogue with the Muslims. The Catholic clergy in the country linked its religious activity close to the policy of the Protectorate, in the hope of succeeding in returning to the ancient “greatness of the African Church”, as the Eucharistic Congress in Carthage in 1930 made quite clear. The Congress itself planted the first seed in the twentyfive- year struggle that led the Tunisian population to independence in 1956 and the founding of the Republic in 1957. The conquest of independence and the ‘Modus vivendi’ marked a profound change in the situation and led to an inversion of roles: the Catholic community was given the right to exist only on the condition that it should not interfere in Tunisian society. The political project of Bourguiba, who led the Republic from 1957 to 1987, aimed to create a strongly egalitarian society, with a separation between political and religious powers. In particular, in referring to the Church, he appeared as a secularist with no hostility towards the Catholics who were, however, considered as “cooperators”, welcome so long as they were willing to place their skills at the service of the construction of the state. So, in the catholic Community was a tension between the will of being on the side of the country and that of conserving a certain distance from it and not being an integral part of it. In this process of reflection, the role of the Second Vatican Council was fundamental: it spread the idea of a Church open to the world and the other religions, in particular to Islam: the teaching of the Council led the congregations present in the country to accept the new condition. This new Church that emerged from the Council saw some important events in the process of “living together”, of “cultural mixing” and the search for a common ground between different realities. The almost contemporary arrival of Arab bishops raised awareness among the Tunisians of the existence of Christian Arabs and, at the same time, the Catholic community began considering their faith in a different way. In the last twenty years the situation has continued to change. Side by side with the priests present for decades or even those born there, some new congregations have begun to operate, albeit in small numbers: they have certainly revitalized the community of the faithful, but they sometimes appear more devoted to service “within” the Church, than to services for the population, and are thus characterized by exterior manifestations of their religion. This sort of presence has made it possible for Bourguiba's successor, Ben Ali (president from 1987 to 2011), to practice forms of tolerance even more clearly, but always limited to formal relations; the Tunisians are still far from having a real understanding of the Catholic reality, with certain exceptions connected to relations on a personal and not structured plane, as was the case in the previous period. The arrival of a good number of young people from sub-Saharan Africa, most of all students, belonging to the JCAT, and personnel of the BAD has “Africanized” the Church in Tunisia and has brought about an increase in Christians' exterior manifestations; but this is a visibility that is not blatant but discreet, with the implicit risk of the Church continuing to be perceived as a sort of exterior body, alien to the country; nor can we say, lacking proper documentation, how it will be possible to build a bridge between different cultures through the “accompaniment” of Christian wives of Tunisians. Today, the Church is living in a country that has less and less need of it; its presence, in the schools and in health facilities, is extremely reduced. And also in other sectors of social commitment, such as care for the disabled, the number of clergymen involved is quite small. The ‘revolution’ in 2011 and the later developments up to the present have brought about another socio-political change, characterized by a climate of greater freedom, but with as yet undefinable contours. This change in the political climate will inevitable have consequences in Tunisia’s approach to religious and cultural minorities, but it is far too soon to discuss this on the historical and scientific planes.