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 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.
Dopaminergic compounds often affect the unlearned behaviors of preweanling and adult rats differently, although the brain regions underlying these age-dependent behavioral effects have not been specified. A candidate brain region is the dorsal caudate-putamen (CPu); thus, a goal of the present study was to determine whether D1 and D2 receptors in the dorsal CPu are capable of modulating the unlearned behaviors of preweanling rats. In Experiments 1 and 2, selective and nonselective dopamine agonists were bilaterally microinjected into the dorsal CPu on postnatal day (PD) 18 and both locomotor activity and stereotypy were measured. In Experiment 3, the functional coupling of D1 and D2 receptors was assessed by microinjecting the D1 agonist SKF-82958 and the D2/D3 agonist quinpirole either alone or in combination. In Experiments 4 and 5, quinpirole and the D1 receptor antagonist SCH-23390, or SKF-82958 and the D2 receptor antagonist raclopride, were co-administered into the dorsal CPu to further assess whether a functional D1 or D2 receptor system is necessary for the expression of quinpirole- or SKF-82958-induced behaviors. Results showed that selective stimulation of D1 or D2 receptors in the dorsal CPu increased both the locomotor activity and stereotypy of preweanling rats. Receptor coupling was evident on PD 18 because co-administration of a subthreshold dose of SKF-82958 and quinpirole produced more locomotor activity than either agonist alone. Lastly, the dopamine antagonist experiments showed that both D1 and D2 receptor systems must be functional for SKF-82958- or quinpirole-induced locomotor activity to be fully manifested. When the present data are compared to results from non-ontogenetic studies, it appears that pharmacological manipulation of D1 and D2 receptors in the dorsal CPu affects the behavior of preweanling and adult rats in a generally similar manner, although some important age-dependent differences are apparent. For example, D1 and/or D2 agonists preferentially induce locomotor activity, and not intense stereotypy, in younger animals.
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 D2High 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% dimethylsulphoxide, DMSO) were 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 D2High receptors using [3H]-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 D2High receptors. Regardless of pretreatment condition (i.e., DMSO or EEDQ), preweanling rats had a greater percentage of D2High 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 D2High receptors.
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