Studies on the role of dopamine D1 receptors in the development and expression of MDMA-induced behavioral sensitization in rats.
BACKGROUND
There is a large body of evidence indicating that the mesoaccumbens dopamine pathway is critically involved in the expression of behavioral sensitization to amphetamine and cocaine, but its role in the development of sensitization to psychostimulants is not that sound. Very few studies, however, have examined the role of dopamine transmission in 3,4-methylenedioxymethamphetamine (MDMA)-induced sensitization.


OBJECTIVE
The effects of the D1 receptor antagonist SCH 23390 on the development and expression of MDMA-induced behavioral sensitization were investigated in rats.


METHODS
During the development phase of sensitization, SCH 23390 was administered 15 min before every administration of MDMA. After 12 days of withdrawal, a MDMA challenge dose was given and locomotor activity was measured. In separate experiments, 15 min before the challenge injection of MDMA, SCH 23390 was administered either systemically or directly into the core of the nucleus accumbens (NAc) of MDMA-pretreated rats.


RESULTS
SCH 23390 did not prevent the development of MDMA-induced behavioral sensitization but completely blocked the expression when given before the challenge dose of MDMA. The same results were obtained when SCH 23390 was locally applied into the core of the NAc.


CONCLUSIONS
The present data suggest that D1 receptor stimulation is not critical for the development of long-term MDMA sensitization, in agreement with what has been reported for cocaine. By contrast, expression of sensitization depends on the activation of D1 receptors located in the NAc core.
Ramos
María
M
Department of Pharmacology, School of Medicine, University of Navarra, C/Irunlarrea, 1, 31008 Pamplona, Spain.
Goñi-Allo
Beatriz
B
Aguirre
Norberto
N
D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D018817:N-Methyl-3,4-methylenedioxyamphetamine