Ricerc@Sapienza

Previous studies have shown that rats trained to self-administer heroin and cocaine exhibit opposite preferences, as a function of setting, when tested in a choice paradigm. Rats tested at home prefer heroin to cocaine, whereas rats tested outside the home prefer cocaine to heroin. Here, we investigated whether drug history would influence subsequent drug preference in distinct settings. Based on a theoretical model of drug-setting interaction, we predicted that regardless of drug history rats would prefer heroin at home and cocaine outside the home.

Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug reward to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and, until recently, an animal model of this human condition did not exist.

In astrocytes, the intracellular calcium (Ca2+) signaling mediated by activation of metabotropic glutamate receptor 5 (mGlu5) is crucially involved in the modulation of many aspects of brain physiology, including gliotransmission. Here, we find that the mGlu5-mediated Ca2+ signaling leading to release of glutamate is governed by mGlu5 interaction with Homer1 scaffolding proteins. We show that the long splice variants Homer1b/c are expressed in astrocytic processes, where they cluster with mGlu5 at sites displaying intense local Ca2+ activity.