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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 self\u2010administration 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\u2010administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex\u2010to\u2010nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose\u2010dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the <jats:italic>in vivo<\/jats:italic> paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self\u2010administration. Furthermore, BZY\u2010induced Long Term Depression (LTD)\u2010like responses in the prelimbic cortex\u2010to\u2010nucleus accumbens 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.<\/jats:p>","DOI":"10.1111\/adb.12516","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T10:06:37Z","timestamp":1492769197000},"page":"610-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intravenous self\u2010administration of benzydamine, a non\u2010steroidal anti\u2010inflammatory drug with a central cannabinoidergic mechanism of action"],"prefix":"10.1111","volume":"23","author":[{"given":"Riccardo","family":"Avvisati","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Italy"},{"name":"Sussex Addiction Research and Intervention Centre (SARIC), School of Psychology University of Sussex  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