Behavioral effects of dopamine receptor inactivation during the adolescent period: age-dependent changes in dorsal striatal D2(High) receptors.

RATIONALE: Dopamine (DA) receptor inactivation produces opposing behavioral effects across ontogeny. For example, inactivating DA receptors in the dorsal striatum attenuates DA agonist-induced behaviors of adult rats, while potentiating the locomotor activity of preweanling rats. OBJECTIVE: The purpose of this study was to determine if DA receptor inactivation potentiates the DA agonist-induced locomotor activity of adolescent rats and whether alterations in D2(High) receptors are responsible for this effect. METHODS: In the behavioral experiment, the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or its vehicle (100 % dimethyl sulfoxide, DMSO) was bilaterally infused into the dorsal striatum on postnatal day (PD) 39. On PD 40, adolescent rats were given intrastriatal infusions of the DA agonist R(-)-propylnorapomorphine (NPA) or vehicle and locomotor activity was measured for 40 min. In the receptor binding experiment, rats received IP injections of EEDQ or DMSO (1:1 (v/v) in distilled water) on PD 17, PD 39, or PD 84. One day later, striatal samples were taken and subsequently assayed for D2-specific binding and D2(High) receptors using [(3)H]-domperidone. RESULTS: Unlike what is observed during the preweanling period, EEDQ attenuated the NPA-induced locomotor activity of adolescent rats. EEDQ reduced D2 receptor levels in the dorsal striatum of all age groups while increasing the proportion of D2(High) receptors. Regardless of pretreatment condition (i.e., DMSO or EEDQ), preweanling rats had a greater percentage of D2(High) receptors than adolescent or adult rats. CONCLUSIONS: DA receptor inactivation affects the behaviors of preweanling and older rats differently. The DA supersensitivity exhibited by EEDQ-treated preweanling rats may result from an excess of D2(High) receptors.

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.