The Effects of Acute and Binge 3,4-methylenedioxymethamphetamine (MDMA) Exposure on Learning and Memory in Rats

摘要

When rats are administered acute doses of MDMA they produce significantly more reference memory errors than working memory errors in the partially baited radial arm maze (Kay et al, 2009). The potential role of serotonin and dopamine in this effect was examined by administering the serotonin agonist Citalopram and the dopamine agonist GBR12909. GBR12909 produced significantly more reference memory errors, while Citalopram tended to produce more working memory errors. Administration of the D1 agonist A68930 and the D2 agonist Quinpirole predominantly produced reference memory errors, but to a lesser extent than acute MDMA administration. Low doses of both drugs produced a synergistic effect, more similar to that seen with acute MDMA administration. These findings suggest dopamine plays a role in the reference memory effect seen with MDMA exposure in the partially baited radial maze.In the second half of the thesis binge regimes of MDMA (4 x 10mg/kg) were administered to rats. When there was a gap of eight weeks between dosing and training the ability to acquire the radial arm maze was not significantly impaired. When this MDMA regime was repeated with a three-day gap between dosing and training it produced a significant but transient deficit in performance. When later challenged with acute doses of MDMA (4.0 mg/kg) the binge treated rats were less impaired than saline controls indicating drug tolerance. In an additional study that used a three-day delay between dosing and training a significant impairment in task acquisition was found. This deficit appeared to be long-term as the MDMA treated rats were impaired when the rules of task were changed suggesting a deficit in cognitive flexibility. Again when subjects were challenged with acute MDMA there was evidence of drug tolerance. The final study examined the effects of repeated MDMA exposure on task acquisition by administering acute doses of MDMA or saline once a week after rats had previously been treated with either a binge regime of MDMA or saline. MDMA exposure significantly impaired task acquisition and produced residual drug effects in the binge treated MDMA group the day after acute drug administration. However evidence of behavioural tolerance in this study was mixed due to a floor effect where performance of the binge MDMA group was so poor at the beginning of the study.In conclusion MDMA exposure impaired accuracy with reference memory processes were more affected than working memory processes. The underlying nature of this impairment remains unclear but it may be due to a long-term memory deficit, an impairment in understanding task rules or a perseverative pattern of responding. These findings imply human Ecstasy users may show deficits in acquiring information and may experience deficits in cognitive flexibility