Hughes, Katherine M.

Widespread use of the illicit drug ecstasy (MDMA or 3,4-
Methylenedioxymethamphetarnine) and the possible neurological damage caused by its
abuse is disconcerting. This study examined possible cognitive impairments in ecstasy
users while controlling for polydrug use. The CANT AB neuropsychological tests was
used to test working memory capacity, immediate and delayed perceptual matching,
shifting of attention, episodic memory, and learning in current and previous ecstasy users
compared to non-ecstasy polydrug users. The prediction that current and heavy previous
ecstasy users would perform worse on the neuropsychological tests, when compared to
polydrug control group, denoting neurological damage was not confirmed. The previous
light ecstasy users' performance was also equivalent to the poly drug control group,
suggesting that excessive ecstasy use is required to reveal cognitive impairments .. The
results suggest that the amount of ecstasy consumed by the participants did not lead to
cognitive impairments in the brain regions investigated and supports a 'moderation idea'.

The purpose of this study was to determine whether prior sensitization of stereotypy interferes with the development and retention of tolerance to amphetamine-induced hypophagia. Rats were given intermittent injections of either amphetamine to induce sensitization of stereotypy, or saline. Both sensitized and nonsensitized groups became tolerant to drug-induced hypophagia to the same degree. Such tolerance was accompanied by a decrease in the frequency of stereotyped movements while milk was available. After a 4 wk drug withdrawal period, both groups lost tolerance and displayed more intense stereotypy than they had prior to drug withdrawal. Therefore, sensitization of stereotypy did not retard the development of tolerance. However, the loss of tolerance following drug withdrawal may have been due to the development of more intense stereotypy and/or the "unlearning" of previously acquired strategies for suppressing stereotypy.

The purpose of this study was to determine whether behavioral contingencies or pharmacological exposure governs the development, loss and retention of tolerance to amphetamine-induced hypophagia in rats. In Experiment 1, rats that had developed tolerance by learning to suppress stereotypy that interfered with feeding from a bottle were divided into three groups to test the retention of tolerance. The Before group received injections of amphetamine (2.0 mg/kg) before access to milk, the After group received injections of amphetamine after access to milk, and the Saline group received injections of saline before access to milk. Both the After and Saline groups lost tolerance when later tested with amphetamine before milk tests. Thus, the loss of tolerance was not a function of drug withdrawal, because drug exposure remained constant in the After group. When milk reward was obtained noncontingently, tolerance was lost even though pharmacological exposure was maintained. Behavioral strategies that were learned while intoxicated were replaced with new learning when the contingencies were changed. Experiment 2 determined that tolerance loss was a function of new learning and not simply ingesting milk in the unintoxicated state. Bottle-fed tolerant rats were given amphetamine prior to intraoral feeding of milk during a retention interval. Subsequent testing with amphetamine in the bottle condition revealed that tolerance was lost. Because the cannula feeding condition does not require suppression of stereotypy, milk reward was available noncontingently in the intoxicated state and tolerance was lost even though drug exposure was maintained. In Experiment 3 rats were given chronic amphetamine injections and intraoral feeding. Subsequent tests with amphetamine and bottle feeding revealed that no tolerance developed. These results demonstrate that even when ingestion occurs in the intoxicated state, no tolerance develops if milk reward is available noncontingently. Animals that drank intraorally were not tolerant when tested in the bottle condition.