(+) 3,4-methylenedioxymethamphetamine ('ecstasy') transiently increases striatal 5-HT1B binding sites without altering 5-HT1B mRNA in rat brain.

(+) 3,4-Methylenedioxymethamphetamine (MDMA) is a psychedelic drug of abuse that causes selective degeneration of serotonergic fibers of dorsal raphe neurons that project throughout the forebrain. Previous studies using pharmacological and behavioral approaches suggested that MDMA treatment leads to desensitization of 5-HT1B receptors. We proposed to test whether this occurs by downregulation of 5-HT1B messenger RNA in dorsal raphe, striatum or CA1 hippocampal neurons and/or 5-HT1B binding site density in hippocampus and basal ganglia. In Experiment I, rats were treated with MDMA using several dosing protocols (2.5 or 10 mg kg-1 day-1 s.c. given a single time or twice daily for 4 days). The animals were killed 24 h after the last dose. [3H]-citalopram binding to serotonin transporters in hippocampus was reduced in the high dose protocol, indicating degeneration of forebrain serotonergic fibers. Despite the extensive reduction in serotonergic content, 5-HT1B mRNA did not change from control levels in any region when measured by in situ hybridization. [125I]-Iodocyanopindolol binding to 5-HT1B sites in hippocampus was also not changed. In Experiment II, high dose MDMA had no effect on 5-HT1B mRNA in any brain region either 1 or 14 days after treatment. However, [125I]-iodocyanopindolol binding more than doubled in striatum 1 day after MDMA treatment but returned to control levels by 14 days. This may have been a transient compensation to early neuronal damage caused by MDMA exposure. These results suggest that previously described changes in 5-HT1B function following MDMA treatment involve only posttranscriptional changes in receptor regulation and do not alter 5-HT1B mRNA levels.

Selective access in cued recall: the roles of retrieval cues and domains of encoding.

The purpose of these experiments was to determine whether retrieval access in cued recall can be selectively restricted to a single domain of encoding when information has been encoded within two domains as different as word sound and word meaning. In Experiment 1, the subjects studied pairs of rhyming words differing in rhyme set size under verbal-repetition or interactive-imagery instructions. Recall was cued with study-context rhymes, with extralist rhymes, or with extralist associates. The results indicated that rhyme set size and instructional effects were found no matter how recall was cued, indicating that both domains of encoding were always accessed. In Experiment 2, potential effects of study time and overt naming of the test cues were explored. These results indicated that both domains of encoding were accessed, except when long study times were available and subjects did not have to name the rhyme test cues. Rhyme set-size effects were eliminated under these conditions, suggesting that selective access to encoded meaning is possible in cued recall. Retrieval access in this task appears to be more controlled by domains of encoding than by information directly available in the cue, and access to encoded information can be restricted to a single domain.

Encoding strategy and sensory and semantic interference.

Studies were designed to compare the effects of encoding strategies on two types of interference, sensory and semantic. Paired-associate lists were learned under instructional sets encouraging interactive imagery or repetitious rehearsal. Sensory interference was created by mispairing rhymes and semantic interference was produced by mispairing associatively related words. In control lists word pairs were unrelated. The results indicated that encoding strategy did not influence amounts of sensory and semantic interference. Mispairing rhymes produced the same amount of confusion as mispairing associates whether pairs were encoded through interaction imagery or through repetitious rehearsal. These effects were found with both short and long encoding intervals. The findings are inconsistent with the idea that encoding operations or strategies applied to word pairs completely determine the type of code activated for those pairs. Both sensory and semantic codes appear to be activated under each kind of encoding strategy.