Different patterns of administration modulate propensity of methadone and buprenorphine to promote locomotor sensitization in mice

Abstract

Following chronic administration of morphine a locomotor sensitization is usually observed. This behavioral sensitization is influenced by numerous factors including the administration pattern. While methadone and buprenorphine are the two main treatments for opioid dependence, literature about their ability to promote long-term sensitization after chronic exposure/withdrawal are scarce considering the long-term treatments used in patients. In this study we investigated the propensity of these two opioids to promote behavioral sensitization using different patterns of administration. Mice were treated with escalating doses of methadone or buprenorphine during 5 days given either once (binge) or three times a day (TTD). After 1-, 7-, 14- and 35-days washout period, animals were challenged with either morphine or the opioid used for the chronic treatment to evaluate heterologous or homologous sensitization, respectively. While methadone produced homologous and heterologous sensitization either with the binge or the TTD regimen over the whole period studied, buprenorphine induced a transient heterologous locomotor sensitization on day 14 only with the binge administration. Our data evidenced a different ability of methadone and buprenorphine to produce behavioral sensitization and that the pattern of drug exposure determined the expression of this phenomenon.