Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine.
Continuous infusion of cocaine produces partial behavioral tolerance to its locomotor activating effects, while daily injections produce sensitization. Methylphenidate binds with a similar affinity to cocaine at the dopamine transporter, but has a much lower affinity for the serotonin transporter than does cocaine. This study was done to compare the effects of chronic methylphenidate with chronic cocaine. The pattern of locomotor activity over a 7 day treatment period was significantly different from cocaine. Methylphenidate elevated activity on each day, compared to saline, yet neither tolerance to a continuous infusion of the drug, nor sensitization to repeated daily injections was produced. We have previously shown that neither of these treatments with cocaine produces significant alterations in dopamine transporter density 1 day after the end of treatment. In contrast, methylphenidate injections significantly decreased dopamine transporters in rostral caudate putamen, with no change in nucleus accumbens. Continuous infusion of methylphenidate had no effect on dopamine transporters in either brain region. These findings provide further evidence that different classes of dopamine uptake inhibitors may interact with the dopamine transporter in qualitatively different manners. Furthermore, it is possible that the inhibition of serotonin uptake by cocaine may contribute to the adaptations in behavioral activity that are seen during chronic treatment.
Psychobiology Section, National Institute on Drug Abuse, Division of Intramural Research, Baltimore, MD 21224, USA. sizenwas@newssun.med.miami.edu
S
S
Izenwasser
A E
AE
Coy
B
B
Ladenheim
R J
RJ
Loeloff
J L
JL
Cadet
D
D
French
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000378:metabolism / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008774:Methylphenidate; D003042:Cocaine