We report here that the susceptibility to relapse into drug-seeking behavior is drug-specific and setting-specific, confirming the crucial role played by drug, set, and setting interactions in drug addiction.

RationaleClinical and preclinical evidence indicates that the setting of drug use affects drug reward in a substance-specific manner. Heroin and cocaine co-abusers, for example, indicated distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home. Similar results were obtained in rats that were given the opportunity to self-administer intravenously both heroin and cocaine.ObjectivesThe goal of the present study was to investigate the possibility that the positive affective state induced by cocaine is enhanced when the drug is taken at home relative to a non-home environment, and vice versa for heroin.MethodsTo test this hypothesis, we trained male rats to self-administer both heroin and cocaine on alternate days and simultaneously recorded the emission of ultrasonic vocalizations (USVs), as it has been reported that rats emit 50-kHz USVs when exposed to rewarding stimuli, suggesting that these USVs reflect positive affective states.ResultsWe found that Non-Resident rats emitted more 50-kHz USVs when they self-administered cocaine than when self-administered heroin whereas Resident rats emitted more 50-kHz USVs when self-administering heroin than when self-administering cocaine. Differences in USVs in Non-Resident rats were more pronounced during the first self-administration (SA) session, when the SA chambers were completely novel to them. In contrast, the differences in USVs in Resident rats were more pronounced during the last SA sessions.ConclusionThese findings indicate that the setting of drug taking exerts a substance-specific influence on the ability of drugs to induce positive affective states.

Benzydamine (BZY) is a non-steroidal anti-inflammatory drug (NSAID) used for the topical treatment of inflammations of the oral and vaginal mucosa. Virtually nothing is known about the central pharmacological actions of BZY. Yet, there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat selfadministration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on Prelimbic Cortexto-Nucleus Accumbens (PLCx-NAcc) glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential (fEPSP) amplitude and Paired Pulse Ratio (PPR), suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin selfadministration. Furthermore, BZY-induced LTD-like responses in the PLCx-NAcc circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential.3

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Although obsessive–compulsive disorder (OCD) and the conduct disorders (CD) express a contrasting symptomatology, they could represent different answers to a common matrix about morality. In the literature, some theoretical models describe people with OCD as individuals who experience high levels of responsibility and guilt. On the other hand, adolescents with a CD are described as if they do not feel guilty at all or consider anti-social purposes as more important than existing moral purposes. The aims of this study were to investigate the role of forgiveness in responsibility and guilt levels and to test whether this putative relation was influenced by tendencies towards obsessive–compulsive problems (OCP) or conduct problems (CP). In total, 231 adolescents aged between 16 and 18 years were self-assessed using a Youth Self-Report, Child Responsibility Attitudes Questionnaire, Heartland Forgiveness Scale, and Test Of Self-Conscious Affect. The results show that self-forgiveness predicted responsibility levels, while guilt was predicted by self-forgiveness and situation-forgiveness. Moreover, mediation analyses revealed that the effects of OCP on responsibility and guilt were mediated by self-forgiveness and situation-forgiveness. Regarding CP, no mediated effects were found. In conclusion, lower proneness to forgive increases responsibility and guilt, and this is particularly evident in subjects with higher levels of OCP.