Psychopharmacology

The purpose of this study was to relate different levels of brain catecholamine& with differential emotional responding. Dopa
was used to facilitate synthesis of NE; R-methyldopa and Dibenxyline
were used to inhibit NE synthesis.
Sa were 80 male Holtzman rats, 85 and 55 days old. The testing
apparatus was a runway with a grid floor and plexiglas& sides, with
a water bottle au one end. After deprived Sa were shaped to run
for water, shock was delivered to the second half of the grid floor.
Sa were injected according to pre-assigned group schedules and
replaced in the testing apparatus 5 hours later. The latency to
the first drinking response was used as a measure of the strength
of the emotional response. Effects of the drugs on general activity
and drinking rate were also measured.
Dopa was found to increase the latency significantly over that
of the controls. Dibenzyline and R-methyldopa did not decrease the
latency relative to the controls. However, the potential of these
drugs was indicated. The drugs were also found to effect general
activity and drinking. Results implicate NE as a mediator of
emotional responding.

3,4-methlenedioxymethamphetamine (MDMA), the main constituent of Ecstasy, is a ring-substituted amphetamine commonly abused in recreational users. High doses of MDMA determined by allometric scaling produce serotonin (5-HT) axon deneveration. Studies suggest that this interspecies scaling does not reflect human use. An 'effects' scale comparing similar behavioral and physiological effects between species has been postulated as more accurate for translational studies. Experiment 1 examined the effects of MDMA on serotonergic forebrain innervation using immunohistochemical labeling targeting the serotonin transporter protein (SERT). Experiments 2 and 3 examined low and high doses of MDMA on spatial memory, prefrontal functioning, and serotonergic neurotoxicity using 'effects' scaling. Long Evans rats were given MDMA regimens of: chronic low dose (daily injections of 1.5 mg/kg for 10 days); binge low dose (2 days of 4 x 1.5 mg/kg spaced 2 hours apart), binge high dose (2 x 7.5 mg/kg sp aced 2 hours apart). Acquisition, retention, and spatial reversal (SR) were measured in a water maze task. A 2.0 mg/kg MDMA drug challenge was then given prior to a serial spatial reversal (SSR) task to assess performance while under the effect of the drug. Attentional set shifting and behavioral flexibility were assessed in an intradimensional extradimensionl (IED) task using odor/texture discriminations. MDMA chronic and binge low doses did not impair water maze or IED performance and produced no reductions in SERT expression. MDMA binge high dose resulted in significant reductions of SERT density in the prefrontal cortex, striatum, cortical mantle, hippocampus, amygdala, and many thalamic nuclei. Despite prominent 5-HT denervation, water maze performance was unaffected. Selective impairment in behavioral flexibility on the IED test was found.