Behavioral effects of dopamine receptor inactivation in the caudate-putamen of preweanling rats: role of the D2 receptor.

Rationale: 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.