Tags

Type your tag names separated by a space and hit enter

MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor.
J Psychopharmacol. 2008 Mar; 22(2):187-202.JP

Abstract

Human MDMA (R,S-3,4-methylenedioxymethamphetamine) users display selective cognitive deficits after acute MDMA exposure, frequently attributed to serotonin deficits. We postulated that MDMA will compromise executive function in primates and that an inhibitor of the serotonin transporter (SERT) and the norepinephrine transporter (NET) but not the dopamine (DAT) transporter, will prevent impairment. The potencies of DAT/NET, NET and SERT inhibitors to block transport of [(3)H]MDMA and [(3)H]monoamines were compared in vitro. Subsequently, cynomolgus monkeys (Macaca fasicularis) were trained to stable performance in a reversal learning task. Effects of once-weekly oral or i.m. dose of MDMA (1.5 mg/kg, n = 4) on performance were monitored, alone or after pretreatment with inhibitors of the SERT, DAT or NET (prior to i.m. MDMA). 1) Drug potencies for blocking [(3)H]MDMA or [(3)H]monoamine transport were not consistent; 2) Oral MDMA increased error rates in a cognitive task for up to three days following exposure, whereas intramuscular MDMA prevented subjects from performing the cognitive task on the day of administration, but not on subsequent days; 3) The SERT inhibitor citalopram and the NET inhibitor desipramine, but not the DAT/NET inhibitor methylphenidate, reversed the effects of MDMA on task performance and mandibular movements induced by i.m. MDMA and 4) MDMA altered sleep latency. Oral MDMA impairs executive function in monkeys for several days, a finding of potential relevance to MDMA consumption by humans. Reversal of impaired executive function by a NET inhibitor implicates the NET and norepinephrine in MDMA-induced cognitive impairment and may be relevant to therapeutic strategies.

Authors+Show Affiliations

Department of Psychiatry, Harvard Medical School and Division of Neurochemistry, New England Primate Research Center, Southborough, MA 01772-9102, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18308800

Citation

Verrico, Christopher D., et al. "MDMA-induced Impairment in Primates: Antagonism By a Selective Norepinephrine or Serotonin, but Not By a Dopamine/norepinephrine Transport Inhibitor." Journal of Psychopharmacology (Oxford, England), vol. 22, no. 2, 2008, pp. 187-202.
Verrico CD, Lynch L, Fahey MA, et al. MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor. J Psychopharmacol (Oxford). 2008;22(2):187-202.
Verrico, C. D., Lynch, L., Fahey, M. A., Fryer, A. K., Miller, G. M., & Madras, B. K. (2008). MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor. Journal of Psychopharmacology (Oxford, England), 22(2), 187-202. https://doi.org/10.1177/0269881107083639
Verrico CD, et al. MDMA-induced Impairment in Primates: Antagonism By a Selective Norepinephrine or Serotonin, but Not By a Dopamine/norepinephrine Transport Inhibitor. J Psychopharmacol (Oxford). 2008;22(2):187-202. PubMed PMID: 18308800.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MDMA-induced impairment in primates: antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor. AU - Verrico,Christopher D, AU - Lynch,Laurie, AU - Fahey,Michele A, AU - Fryer,Ashley-Kay, AU - Miller,Gregory M, AU - Madras,Bertha K, Y1 - 2008/02/28/ PY - 2008/3/1/pubmed PY - 2008/8/19/medline PY - 2008/3/1/entrez SP - 187 EP - 202 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 22 IS - 2 N2 - Human MDMA (R,S-3,4-methylenedioxymethamphetamine) users display selective cognitive deficits after acute MDMA exposure, frequently attributed to serotonin deficits. We postulated that MDMA will compromise executive function in primates and that an inhibitor of the serotonin transporter (SERT) and the norepinephrine transporter (NET) but not the dopamine (DAT) transporter, will prevent impairment. The potencies of DAT/NET, NET and SERT inhibitors to block transport of [(3)H]MDMA and [(3)H]monoamines were compared in vitro. Subsequently, cynomolgus monkeys (Macaca fasicularis) were trained to stable performance in a reversal learning task. Effects of once-weekly oral or i.m. dose of MDMA (1.5 mg/kg, n = 4) on performance were monitored, alone or after pretreatment with inhibitors of the SERT, DAT or NET (prior to i.m. MDMA). 1) Drug potencies for blocking [(3)H]MDMA or [(3)H]monoamine transport were not consistent; 2) Oral MDMA increased error rates in a cognitive task for up to three days following exposure, whereas intramuscular MDMA prevented subjects from performing the cognitive task on the day of administration, but not on subsequent days; 3) The SERT inhibitor citalopram and the NET inhibitor desipramine, but not the DAT/NET inhibitor methylphenidate, reversed the effects of MDMA on task performance and mandibular movements induced by i.m. MDMA and 4) MDMA altered sleep latency. Oral MDMA impairs executive function in monkeys for several days, a finding of potential relevance to MDMA consumption by humans. Reversal of impaired executive function by a NET inhibitor implicates the NET and norepinephrine in MDMA-induced cognitive impairment and may be relevant to therapeutic strategies. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/18308800/MDMA_induced_impairment_in_primates:_antagonism_by_a_selective_norepinephrine_or_serotonin_but_not_by_a_dopamine/norepinephrine_transport_inhibitor_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881107083639?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -