Document Detail

Microinjection of muscimol into the dorsomedial hypothalamus suppresses MDMA-evoked sympathetic and behavioral responses.
MedLine Citation:
PMID:  18586013     Owner:  NLM     Status:  MEDLINE    
When given systemically to rats and humans, the drug of abuse 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) elicits hyperthermia, hyperactivity, tachycardia, and hypertension. Chemically stimulating the dorsomedial hypothalamus (DMH), a brain region known to be involved in thermoregulation and in stress responses, causes similar effects. We therefore tested the hypothesis that neuronal activity in the DMH plays a role in MDMA-evoked sympathetic and behavioral responses by microinjecting artificial CSF or muscimol, a neuronal inhibitor, into the DMH prior to intravenous infusion of saline or MDMA in conscious rats. Core temperature, heart rate, mean arterial pressure and locomotor activity were recorded by telemetry every minute for 120 min. In rats previously microinjected with CSF, MDMA elicited significant increases from baseline in core temperature (+1.3+/-0.3 degrees C), locomotion (+50+/-6 counts/min), heart rate (+142+/-16 beats/min), and mean arterial pressure (+26+/-3 mmHg). Microinjecting muscimol into the DMH prior to MDMA prevented increases in core temperature and locomotion and attenuated increases in heart rate and mean arterial pressure. These results indicate that neuronal activity in the DMH is necessary for the sympathetic and behavioral responses evoked by MDMA.
Daniel E Rusyniak; Maria V Zaretskaia; Dmitry V Zaretsky; Joseph A DiMicco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-06-14
Journal Detail:
Title:  Brain research     Volume:  1226     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-15     Completed Date:  2009-01-07     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  116-23     Citation Subset:  IM    
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MeSH Terms
Adrenergic Uptake Inhibitors / pharmacology*
Behavior, Animal / drug effects*
Blood Pressure / drug effects
Body Temperature / drug effects
Dorsomedial Hypothalamic Nucleus / drug effects*
Drug Interactions
GABA Agonists / pharmacology*
Heart Rate / drug effects
Locomotion / drug effects
Microinjections / methods
Muscimol / pharmacology*
N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
Rats, Sprague-Dawley
Sympathetic Nervous System / drug effects*,  physiology
Grant Support
C06 RR015481-01/RR/NCRR NIH HHS; DA20484/DA/NIDA NIH HHS; K08 DA020484/DA/NIDA NIH HHS; K08 DA020484-01/DA/NIDA NIH HHS; K08 DA020484-02/DA/NIDA NIH HHS; K08 DA020484-03/DA/NIDA NIH HHS; NS19883/NS/NINDS NIH HHS
Reg. No./Substance:
0/Adrenergic Uptake Inhibitors; 0/GABA Agonists; 2763-96-4/Muscimol; KE1SEN21RM/N-Methyl-3,4-methylenedioxyamphetamine

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