Behavioral effects of dopamine receptor inactivation in the caudate-putamen of preweanling rats: role of the D2 receptor.
BACKGROUND
Inactivating dopamine (DA) receptors in the caudate-putamen (CPu) attenuates basal and DA agonist-induced behaviors of adult rats while paradoxically increasing the locomotor activity of preweanling rats.


OBJECTIVE
The purpose of this study was to determine (a) whether D1 or D2 receptor inactivation is responsible for the elevated locomotion shown by preweanling rats and (b) whether DA receptor inactivation produces a general state in which any locomotor-activating drug will cause a potentiated behavioral response.


METHODS
Dimethyl sulfoxide (DMSO) or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was bilaterally infused into the CPu on postnatal day (PD) 17. In experiment 1, DA receptors were selectively protected from EEDQ-induced alkylation by pretreating rats with D1 and/or D2 antagonists. On PD 18, rats received bilateral microinjections of the DA agonist R(-)-propylnorapomorphine into the dorsal CPu, and locomotor activity was measured for 40 min. In subsequent experiments, the locomotion of DMSO- and EEDQ-pretreated rats was assessed after intraCPu infusions of the selective DA agonists SKF82958 and quinpirole, the partial agonist terguride, or after systemic administration of nonDAergic compounds.


RESULTS
Experiment 1 showed that EEDQ's ability to enhance the locomotor activity of preweanling rats was primarily due to the inactivation of D2 receptors. Consistent with this finding, only drugs that directly or indirectly stimulated D2 receptors produced a potentiated locomotor response in EEDQ-treated rats.


CONCLUSIONS
These results show that DA receptor inactivation causes dramatically different behavioral effects in preweanling and adult rats, thus providing additional evidence that the D2 receptor system is not functionally mature by the end of the preweanling period.
Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA.
Taleen
T
Der-Ghazarian
Crystal B
CB
Widarma
Arnold
A
Gutierrez
Leslie R
LR
Amodeo
Joseph M
JM
Valentine
Danielle E
DE
Humphrey
Ashley E
AE
Gonzalez
Cynthia A
CA
Crawford
Sanders A
SA
McDougall
D000375:Aging; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D008090:Lisuride / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D014886:Weaning
D000477:Alkylating Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; C006208:dironyl; C009074:N-n-propylnorapomorphine; C000470:EEDQ; C071262:SK&F 82958; D008090:Lisuride; D001058:Apomorphine; D004121:Dimethyl Sulfoxide