A Three-Way Drug Discrimination Study: A Role for DA-Mediated Effects in MDMA's Discriminative Cue Properties

<p>While 3,4-methylenedioxymethamphetamine (MDMA) shares many similarities with amphetamine, previous two choice drug discrimination procedures have shown that substitution between the two substances is inconsistent. Three choice drug discrimination procedures have revealed that MDMA can be discriminated from amphetamine, due to MDMA’s primary influence in releasing 5-HT. Neurochemical evidence had previously suggested that at doses >3.0mg/kg MDMA-induced dopamine (DA) release will increase significantly. In the current study rats were trained to discriminate MDMA from amphetamine and saline. As the dose of MDMA increased beyond the training dose (>1.5mg/kg) MDMA-appropriate responding decreased, while the proportion of amphetamine lever responding increased and eventually surpassed MDMA-appropriate responding at the highest dose (4.5mg/kg). This would indicate an important role for DA mediated influences in MDMA’s discriminative cue properties. Further evidence for this conclusion comes from tests with the D1 antagonist SCH23390 and the D2 antagonist eticlopride which attenuated this effect and also led to a nonsignificant increase in the proportion of saline lever responding. Subsequent tests with the 5-HT2c antagonist RS102221resulted in no significant dose dependent changes, but appeared to reduce MDMA-appropriate responding especially at the training dose. The current findings would suggest that low doses of MDMA are discriminable from amphetamine, however with increasing doses MDMA will be perceived as more “amphetamine-like”. These findings could suggest that at relatively high doses MDMA produces effects that are typically associated with dopamine-releasing drugs, such as high abuse potential.</p>

A Three-Way Drug Discrimination Study: A Role for DA-Mediated Effects in MDMA's Discriminative Cue Properties

<p>While 3,4-methylenedioxymethamphetamine (MDMA) shares many similarities with amphetamine, previous two choice drug discrimination procedures have shown that substitution between the two substances is inconsistent. Three choice drug discrimination procedures have revealed that MDMA can be discriminated from amphetamine, due to MDMA’s primary influence in releasing 5-HT. Neurochemical evidence had previously suggested that at doses >3.0mg/kg MDMA-induced dopamine (DA) release will increase significantly. In the current study rats were trained to discriminate MDMA from amphetamine and saline. As the dose of MDMA increased beyond the training dose (>1.5mg/kg) MDMA-appropriate responding decreased, while the proportion of amphetamine lever responding increased and eventually surpassed MDMA-appropriate responding at the highest dose (4.5mg/kg). This would indicate an important role for DA mediated influences in MDMA’s discriminative cue properties. Further evidence for this conclusion comes from tests with the D1 antagonist SCH23390 and the D2 antagonist eticlopride which attenuated this effect and also led to a nonsignificant increase in the proportion of saline lever responding. Subsequent tests with the 5-HT2c antagonist RS102221resulted in no significant dose dependent changes, but appeared to reduce MDMA-appropriate responding especially at the training dose. The current findings would suggest that low doses of MDMA are discriminable from amphetamine, however with increasing doses MDMA will be perceived as more “amphetamine-like”. These findings could suggest that at relatively high doses MDMA produces effects that are typically associated with dopamine-releasing drugs, such as high abuse potential.</p>

Perception of the Müller–Lyer illusion in guppies

The Müller–Lyer illusion is a well-known distortion illusion that occurs when the spatial arrangement of inducers (i.e., inwards- or outwards-pointing arrowheads) influences a line’s perceived relative length. To date, this illusion has been reported in several animal species but only in 1 teleost fish (i.e., redtail splitfins Xenotoca eiseni), although teleost fish represent approximately 50% of vertebrate diversity. We investigated the perception of this illusion in another teleost fish: guppies Poecilia reticulata, a species that diverged from the redtail splitfin 65 million years ago. The guppies were trained to select the longer between 2 lines; after meeting the learning criterion, illusory trials were presented. Control trials were also arranged to exclude the possibility that their choices were based on potential spatial biases that relate to the illusory pattern. The guppies’ overall performance indicated that they were susceptible to the Müller–Lyer illusion, perceiving the line with the inwards-pointing arrowheads as longer. The performance in the control trials excluded the possibility that the subjects used the physical differences between the 2 figures as the discriminative cue in the illusory trials. Our study suggests that sensibility to the Müller–Lyer illusion could be widespread across teleost fish and reinforces the idea that the perceptual mechanisms underlying size estimation might be similar across vertebrates.

Use of a non-navigational, non-verbal landmark task in children

Two hundred and twenty two children (104 females), 1–8 years of age and young adults, were tested for up to 25 days on five versions of a non-verbal, non-navigational landmark task that had previously been used for monkeys. In monkeys, performance on this task is severely impaired following damage to the parietal cortex. For the basic task, the positive of two identical stimuli concealed a food reward and was designated by spatial proximity of a salient landmark. None of the 1- and 2-year-old children learned the task, i.e., they failed to consistently reach for and displace the positive stimulus in 25 test days. Of the 3-, 4-, and 5- year-old groups, 56%, 70%, and 77% of the children, respectively, mastered the task within 25 days. Children older than 5 and adults rapidly mastered the task. In Experiment #2, all subjects, 1–6 years of age, rapidly mastered a non-relational task when the choice stimulus was attached to the landmark, but the youngest children failed to transfer performance when the landmark was subsequently detached. Children under the age of 5 did not tolerate relational ambiguity as well as adults did. Replications of the first two experiments produced virtually identical results and indicated that the tests have a high degree of reliability. In Experiment #5, there were two distinct proximal landmarks, one of which always designated the positive stimulus. This manipulation did not improve performance of younger children. As compared to results from navigational landmark tasks, results obtained in the Wisconsin General Testing Apparatus (WGTA) indicate a very narrow focus of attention on the response site. Thus, small separations between discriminative cue and response site significantly affect performance, especially in younger children. By comparing the present results with those from monkeys, we speculate that components of the parietal pathways involved with attention and reaching mature between 1 and 5 years of age in children.