Context-dependent behavioural and neuronal sensitization in striatum to MDMA (ecstasy) administration in rats

To investigate the neuronal mechanisms underlying the behavioural alterations that accompany repeated exposure to MDMA (ecstasy), we recorded the activity of > 200 striatal units in response to multiple, intermittent, locomotor‐activating doses (5.0 mg/kg) of MDMA. Rats were treated with once‐daily injections of either saline or MDMA for 5 days when housed in their home cage, followed by a challenge injection 3–5 days later when housed in a recording chamber. Because contextual drug associations might be particularly important to the expression of behavioural sensitization to chronic MDMA, a separate group of rats received repeated injections of MDMA alternately in the recording chamber or home cage, according to the above timeline. A sensitized locomotor response was observed only in rats that had previously experienced MDMA in the context of the recording chamber, and only on the challenge day. These sensitized animals also showed a decreased basal firing rate in neurons that were subsequently excited by MDMA when compared with the same category of neurons earlier in the treatment regimen. This resulted in a greater percentage increase from the baseline firing rate on the challenge day compared with the first and fifth days of treatment, even though this trend was not evident with an analysis of absolute firing rate. These results strongly support a role for context in the expression of MDMA‐induced locomotor sensitization, and implicate striatal involvement in the neurobehavioural changes associated with the repeated use of MDMA.