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All 10 posts Subject: Neuropsychopharmacology 29(7): 1270 2004 ... Please login to post Down

Lilienthal
(Moderator)
08-20-04 19:28
No 526504
User Picture       Neuropsychopharmacology 29(7): 1270 2004 ...
(Rated as: excellent)

Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys

William E. Fantegrossi, William L. Woolverton, Michael Kilbourn, Phillip Sherman, Jie Yuan,
George Hatzidimitriou, George A. Ricaurte, James H. Woods, and Gail Winger

The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on behavior and neurochemistry have not been previously studied in laboratory primates. We investigated the capacity of MDMA and its enantiomers to maintain contingent responding over an extended duration, whether any decrements in the reinforcing effects of these compounds would be observed over time, whether such decrements would be MDMA-selective, and whether any neurochemical correlates could be identified. Animals were previously trained to self-administer cocaine, then exposed to periodic substitutions of various doses of racemic MDMA and its enantiomers; full dose-effect curves were generated for each MDMA compound repeatedly over the duration of the study. After approximately 18 months of MDMA self-administration, drug exposure was halted and after at least 2 months drug abstinence, animals were scanned using positron emission tomography (PET) with the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). Shortly thereafter, animals were euthanized, brains were dissected, and samples were assayed for brain monoamines and their metabolites using high-performance liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing effects of racemic and R(-)-MDMA were reduced over a long series (months) of individual self-administration access periods; the reinforcing effects of S+-MDMA were more resistant to this effect, but were attenuated for one animal. The reinforcing effects of cocaine were not altered by chronic MDMA self-administration, nor was the VMAT binding potential as assessed by PET. Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of MDMA are selectively attenuated by chronic MDMA self-administration, although this behavioral change appears to occur in the absence of any frank neurochemical correlates of toxicity.

Neuropsychopharmacology 29(7): 1270 2004 DOI:10.1038/sj.npp.1300442
Medline (PMID=15039771)

Raad also this comment at MAPS: http://www.maps.org/sys/w3pb.pl?mode=show&type=review&r_id=1

Barium
(Heavyweight Chempion(eer))
08-20-04 22:33
No 526525
      Wow!

If these results can be reproduced then - Eat shit and die Ricaurte! cool

Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!

Antoncho
(Official Hive Translator)
08-21-04 02:20
No 526543
      Hoorray!

Wondered about this for a long time....

Please note though that simply absence of toxicity doesn't imply that there were no "psychiatric" disturbances.

Lilienthal
(Moderator)
08-21-04 08:41
No 526570
User Picture       Ricaurte is a co-author

Barium: Actually George A. Ricaurte is a co-author of that paper smile . (I have now added the authors to the first post).

Barium
(Heavyweight Chempion(eer))
08-21-04 13:16
No 526586
      Shit

Lilly: Whan you said it I looked more thoroughly in the author field and saw his name. Holy shit! blush *tehee*
Well lets see if the dear doctor Ricaurte can, as a good scientist should be able too, say - I was wrong.

Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!

jsorex
(Hive Addict)
08-23-04 18:40
No 526967
User Picture       No neurotransmitter abnormalities.

No neurotransmitter abnormalities. But yet cell death: Post 526882 (methyl_ethyl: "MDMA mediated production of H2O2 in vitro", General Discourse)

Barium
(Heavyweight Chempion(eer))
08-24-04 08:54
No 527069
      Hmm

I would expect a massive destruction of serotonin neurons to cause some "neurotransmittor abnormalities". But hey, that's just me. tongue

Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!

7is
(Hive Bee)
08-24-04 20:37
No 527123
User Picture       Cognitive neurotoxicity?

Because we don't really understand neurochemistry that much, I think that best measurement of neurotoxicity is cognitive tests.

Chimitant
(Newbee)
08-24-04 21:38
No 527134
User Picture       Drug apes

Can someone explain to me why they had to use apes that were on cocaine prior to the MDMA experiments ? I would have expected them to use clean apes to show neurotoxicity effects of MDMA on the brain...And why administer meth at the same time?

(I´m not into this type of studies so forgive me if the questions are stupid or if I misunderstood the article)

A little poison now and then: that makes for agreeable dreams.

Jubrail
(Introspecter)
08-25-04 00:16
No 527161
      Cocaine is a teaching aid

Cocaine, due to its euphoric, yet incredibly tolerable effects, is useful to teach the apes how to self-administer drugs. They will quickly become proficient at drugging themselves with cocaine, as they will immediately administer it often and learn how to do it. MDMA may not be quite desirable and short-acting enough to train a monkey with. Also, cocaine, afaik, has not been shown to have neurotoxic effects, therefore they wouldn't do any brain damage. For that reason, you can participate in clinical brain-scan surveys documenting MDMAs effects if you are also a cocaine user, but not if you use PCP or K.

Rainbows & Butterflies Forever :)

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	All 10 posts		Subject: Neuropsychopharmacology 29(7): 1270 2004 ...		Please login to post		Down


		Lilienthal (Moderator) 08-20-04 19:28 No 526504				Neuropsychopharmacology 29(7): 1270 2004 ... (Rated as: excellent)
						Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys William E. Fantegrossi, William L. Woolverton, Michael Kilbourn, Phillip Sherman, Jie Yuan, George Hatzidimitriou, George A. Ricaurte, James H. Woods, and Gail Winger The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on behavior and neurochemistry have not been previously studied in laboratory primates. We investigated the capacity of MDMA and its enantiomers to maintain contingent responding over an extended duration, whether any decrements in the reinforcing effects of these compounds would be observed over time, whether such decrements would be MDMA-selective, and whether any neurochemical correlates could be identified. Animals were previously trained to self-administer cocaine, then exposed to periodic substitutions of various doses of racemic MDMA and its enantiomers; full dose-effect curves were generated for each MDMA compound repeatedly over the duration of the study. After approximately 18 months of MDMA self-administration, drug exposure was halted and after at least 2 months drug abstinence, animals were scanned using positron emission tomography (PET) with the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). Shortly thereafter, animals were euthanized, brains were dissected, and samples were assayed for brain monoamines and their metabolites using high-performance liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing effects of racemic and R(-)-MDMA were reduced over a long series (months) of individual self-administration access periods; the reinforcing effects of S+-MDMA were more resistant to this effect, but were attenuated for one animal. The reinforcing effects of cocaine were not altered by chronic MDMA self-administration, nor was the VMAT binding potential as assessed by PET. Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of MDMA are selectively attenuated by chronic MDMA self-administration, although this behavioral change appears to occur in the absence of any frank neurochemical correlates of toxicity. Neuropsychopharmacology 29(7): 1270 2004 DOI:10.1038/sj.npp.1300442 Medline (PMID=15039771) Raad also this comment at MAPS: http://www.maps.org/sys/w3pb.pl?mode=show&type=review&r_id=1



		Barium (Heavyweight Chempion(eer)) 08-20-04 22:33 No 526525				Wow!
						If these results can be reproduced then - Eat shit and die Ricaurte! Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!



		Antoncho (Official Hive Translator) 08-21-04 02:20 No 526543				Hoorray!
						Wondered about this for a long time.... Please note though that simply absence of toxicity doesn't imply that there were no "psychiatric" disturbances.



		Lilienthal (Moderator) 08-21-04 08:41 No 526570				Ricaurte is a co-author
						Barium: Actually George A. Ricaurte is a co-author of that paper . (I have now added the authors to the first post).



		Barium (Heavyweight Chempion(eer)) 08-21-04 13:16 No 526586				Shit
						Lilly: Whan you said it I looked more thoroughly in the author field and saw his name. Holy shit! tehee Well lets see if the dear doctor Ricaurte can, as a good scientist should be able too, say - I was wrong. Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!



		jsorex (Hive Addict) 08-23-04 18:40 No 526967				No neurotransmitter abnormalities.
						No neurotransmitter abnormalities. But yet cell death: Post 526882 (methyl_ethyl: "MDMA mediated production of H2O2 in vitro", General Discourse)



		Barium (Heavyweight Chempion(eer)) 08-24-04 08:54 No 527069				Hmm
						I would expect a massive destruction of serotonin neurons to cause some "neurotransmittor abnormalities". But hey, that's just me. Severe Aztecoholic and President of Sooty's fanclub - Sooty for President!!



		7is (Hive Bee) 08-24-04 20:37 No 527123				Cognitive neurotoxicity?
						Because we don't really understand neurochemistry that much, I think that best measurement of neurotoxicity is cognitive tests.



		Chimitant (Newbee) 08-24-04 21:38 No 527134				Drug apes
						Can someone explain to me why they had to use apes that were on cocaine prior to the MDMA experiments ? I would have expected them to use clean apes to show neurotoxicity effects of MDMA on the brain...And why administer meth at the same time? (I´m not into this type of studies so forgive me if the questions are stupid or if I misunderstood the article) A little poison now and then: that makes for agreeable dreams.



		Jubrail (Introspecter) 08-25-04 00:16 No 527161				Cocaine is a teaching aid
						Cocaine, due to its euphoric, yet incredibly tolerable effects, is useful to teach the apes how to self-administer drugs. They will quickly become proficient at drugging themselves with cocaine, as they will immediately administer it often and learn how to do it. MDMA may not be quite desirable and short-acting enough to train a monkey with. Also, cocaine, afaik, has not been shown to have neurotoxic effects, therefore they wouldn't do any brain damage. For that reason, you can participate in clinical brain-scan surveys documenting MDMAs effects if you are also a cocaine user, but not if you use PCP or K. Rainbows & Butterflies Forever :)

All 10 posts	End of thread	Top