PMID- 8551999
OWN - NLM
STAT- MEDLINE
DCOM- 19960222
LR  - 20190920
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 17
IP  - 5
DP  - 1995 Sep-Oct
TI  - Behavioral and neurochemical effects of chronic methylenedioxymethamphetamine 
      (MDMA) treatment in rhesus monkeys.
PG  - 531-43
AB  - Effects of chronic treatment with the putative serotonergic neurotoxicant MDMA 
      were assessed in rhesus macaques using behavior in an operant test battery (OTB) 
      designed to model aspects of time estimation, short-term memory, motivation, 
      learning, and color and position discrimination. After an initial acute 
      dose-response assessment, escalating doses of MDMA (0.10-20.0 mg/kg, im, twice 
      daily, for 14 consecutive days at each dose) were administered, followed by three 
      additional acute dose-response assessments. In general, tolerance to MDMA's acute 
      effects was evident in all OTB tasks by the second week of repeated exposure to 
      each individual MDMA dose and as doses escalated. Baseline OTB performance after 
      chronic treatment was not significantly altered. Residual behavioral tolerance to 
      MDMA's acute effects, however, was evident in all OTB tasks but was least 
      pronounced in the motivation task. Monkeys were sacrificed (21 months after 
      chronic treatment) and brains were dissected into several regions for 
      neurochemical analyses. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), 
      dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid 
      (HVA) were analyzed via HPLC. Although MDMA-treated monkeys tended to have lower 
      5-HT concentrations in the frontal cortex, chronic MDMA treatment had no 
      significant effects on 5-HT concentrations in any brain area sampled. Hippocampal 
      5-HIAA concentration, 5-HT uptake sites, and turnover of 5-HT of MDMA-treated 
      monkeys were significantly lower than control values. DA concentrations in the CN 
      of MDMA-treated monkeys were significantly greater than control values. No 
      significant effects on DA concentrations were noted in any other brain area 
      sampled. The absence of significant decreases in 5-HT and the general increase in 
      DA concentrations are dissimilar to neurochemical effects reported after a short 
      course of MDMA treatment at relatively high doses. These data suggest that 
      chronic administration of gradually increasing doses of MDMA results in 
      long-lasting tolerance to the drugs acute effects on the complex brain functions 
      modeled in the OTB. It is uncertain, however, if such tolerance is related to the 
      observed decreases in uptake sites and turnover of 5-HT in the hippocampus of 
      these monkeys.
FAU - Frederick, D L
AU  - Frederick DL
AD  - Division of Neurotoxicology, National Center for Toxicological Research/FDA, 
      Jefferson, AR 72079-9502, USA.
FAU - Ali, S F
AU  - Ali SF
FAU - Slikker, W Jr
AU  - Slikker W Jr
FAU - Gillam, M P
AU  - Gillam MP
FAU - Allen, R R
AU  - Allen RR
FAU - Paule, M G
AU  - Paule MG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Serotonin Agents)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Animals
MH  - Biogenic Monoamines/metabolism
MH  - Brain/drug effects/metabolism
MH  - Conditioning, Operant/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - Homovanillic Acid/metabolism
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Macaca mulatta
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Psychomotor Performance/*drug effects
MH  - Reinforcement Schedule
MH  - Serotonin Agents/*pharmacology
MH  - Time Factors
EDAT- 1995/09/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 0892-0362(95)00013-H [pii]
AID - 10.1016/0892-0362(95)00013-h [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 1995 Sep-Oct;17(5):531-43. doi: 
      10.1016/0892-0362(95)00013-h.