The discriminative stimulus effects of several novel antidepressant drugs were studied in squirrel monkeys trained to discriminate methamphetamine (MA) from saline using conventional drug discrimination procedures. Substitution tests were completed initially with MA (0.03-1.0 mg/kg), prior to testing nomifensine (0.10-3.0 mg/kg), bupropion (0.30-3.0 mg/kg), trazadone (1-17.8 mg/kg), doxepin (0.30-5.6 mg/kg), fluoxetine (1-17.8 mg/kg), citalopram (1-17.8 mg/kg) and sertraline (1-10 mg/kg). For comparison purposes, a number of conventional tricyclic antidepressants (TCA's) were also studied in these monkeys. Fluoxetine, citalopram, sertraline and the TCA's, drugs which primarily inhibit NE or 5-HT uptake, failed to substitute for MA. Partial substitution (50-90% MA-lever responses) was obtained with nisoxetine, trazadone and doxepin, and full substition (>90% MA-lever responses) was observed with bupropion and nomifensine. These results suggest that antidepressants which function primarily as DA uptake inhibitors share discriminative stimulus properties with MA. However, the results with doxepin and trazadone suggest that other monoaminergic systems, particularly the NE system, may also be involved in mediating the MA-like effects of some clinically important antidepressants.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-35
Application #
3718967
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

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