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.
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.
Authors: Richard M Kostrzewa; Karolina Wydra; Malgorzata Filip; Cynthia A Crawford; Sanders A McDougall; Russell W Brown; Dasiel O Borroto-Escuela; Kjell Fuxe; Raul R Gainetdinov Journal: J Pharmacol Exp Ther Date: 2018-06-19 Impact factor: 4.030