Effects of D-Cycloserine Administration on Weekly Nonemotional Memory Tasks in Healthy Participants

Background: The application of weekly doses of D-cycloserine (DCS) to the enhancement of exposure-based treatments has been a particular achievement of translational research. It is not known, however, whether this enhancement effect can be extended to other forms of learning. In this study, we investigated the relative benefit of DCS versus placebo for enhancing nonemotional verbal and nonverbal memory across weekly trials. Methods: We randomized healthy participants to weekly doses of 50 mg DCS or placebo, with 33 participants completing a 5-week protocol. Participants completed baseline neuropsychological evaluation and then 4 subsequent weeks of repeated learning tasks. Results: No improvement was found in immediate or delayed memory following single doses of DCS for the memory tasks repeated on a weekly basis. Trends for an advantage of DCS were evident for novel word lists given each week. Conclusions: The learning tasks in our study were particularly distinct from the extinction learning paradigms that have shown strong DCS effects, and we were unable to demonstrate useful DCS effects with these nonemotional stimuli. Additional research is needed to elucidate the bounds of DCS augmentation effects on therapeutic learning

Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats

BACKGROUND: D-methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats. METHODS: Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1 mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20 mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15 mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30 min after an acute challenge dose of 3.2 mg/kg METH. RESULTS: Active vaccination inhibited the acquisition of METH self-administration under the 0.1 mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05 mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers. CONCLUSIONS: These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration