Dopamine receptor inactivation in the caudate-putamen differentially affects the behavior of preweanling and adult rats

Der-Ghazarian, Taleen; Gutierrez, Arnold; Varela, Fausto A.; Herbert, Matthew S.; Amodeo, Leslie R.; Charntikov, Sergios; Crawford, Cynthia A.; McDougall, Sanders A.

doi:10.1016/j.neuroscience.2012.09.030

Cited by 14 publications

(38 citation statements)

References 68 publications

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“…In adolescent and adult rats, EEDQ minimally elevates the percentage of D2 High receptors while attenuating DA agonist-induced behaviors (Der Ghazarian et al 2012; McDougall et al 2014b). Microinjecting EEDQ into the striatum of preweanling rats, on the other hand, significantly reduces D2 receptor densities, increases the percentage of D2 High receptors, and potentiates cocaine-induced locomotor activity (Der Ghazarian et al 2012, 2014; McDougall et al 2014b). Thus, EEDQ-induced increases in D2 High receptors appear to enhance behavioral sensitivity to cocaine and other DA agonists.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

et al. 2015

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Rationale Responsiveness to acute psychostimulant administration varies across ontogeny. Objective The purpose of the present study was to determine if age-dependent changes in D2High receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats. Methods [3H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2High receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult rats (PD 80). In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20 mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats were habituated to the apparatus on the two days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls. Results Male and female preweanling rats (PD 5–PD 20) had a significantly greater percentage of dorsal striatal D2High receptors than adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive to the behavioral effects of cocaine than the two older age groups. Adolescent and adult rats responded in a generally similar manner, however analysis of the untransformed locomotor activity data suggested that adolescent rats were hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. Conclusions Data from the present study are consistent with the hypothesis that ontogenetic changes in D2High receptors are responsible for age-dependent differences in psychostimulant sensitivity.

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Section: Discussionmentioning

confidence: 99%

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

et al. 2015

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“…Corrected degrees of freedom were rounded to the nearest whole number and are indicated by a superscripted “a”. Prepubescent rats, unlike young mice (Laviola et al, 1994), do not typically exhibit sex differences after DA agonist treatment (Frantz et al, 1996; Bowman et al, 1997; Snyder et al, 1998; Der-Ghazarian et al, 2012). Consistent with these past rat studies, distance traveled data did not differ according to sex, so this variable was not included in the final statistical analyses.…”

Section: Methodsmentioning

confidence: 99%

Repeated aripiprazole treatment causes dopamine D2 receptor up-regulation and dopamine supersensitivity in young rats

et al. 2013

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Aripiprazole is a second-generation antipsychotic that is increasingly being prescribed to children and adolescents. Despite this trend, little preclinical research has been done on the neural and behavioral actions of aripiprazole during early development. In the present study, young male and female Sprague-Dawley rats were pretreated with vehicle, haloperidol (1 mg/kg), or aripiprazole (10 mg/kg) once daily on postnatal days (PD) 10–20. After one, four, or eight days (i.e., on PD 21, PD 24, or PD 28), amphetamine-induced locomotor activity and stereotypy, as well as dorsal striatal D2 receptor levels, were measured in separate groups of rats. Pretreating young rats with aripiprazole or haloperidol increased D2 binding sites in the dorsal striatum. Consistent with these results, dopamine supersensitivity was apparent when aripiprazole- and haloperidol-pretreated rats were given a test day injection of amphetamine (2 or 4 mg/kg). Increased D2 receptor levels and altered behavioral responding persisted for at least eight days after conclusion of the pretreatment regimen. Contrary to what has been reported in adults, repeated aripiprazole treatment caused D2 receptor up-regulation and persistent alterations of amphetamine-induced behavior in young rats. These findings are consistent with human clinical studies showing that children and adolescents are more prone than adults to aripiprazole-induced side-effects, including extrapyramidal symptoms.

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“…In terms of behavioral responsiveness, for example, preweanling and adult rats respond in a nearly opposite manner after pharmacologically-induced DA receptor inactivation. More specifically, microinjecting the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) into the CPu depresses the basal locomotor activity of adult rats, while increasing the locomotion of preweanling rats (Der-Ghazarian et al 2012). This unusual ontogenetic effect is even more prominent after treatment with a nonselective DA receptor agonist, because EEDQ-treated preweanling rats given R-propylnorapomorphine (NPA) infusions into the CPu exhibit significantly more locomotor activity than rats treated with NPA alone (Der-Ghazarian et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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Dopamine receptor inactivation in the caudate-putamen differentially affects the behavior of preweanling and adult rats

Cited by 14 publications

References 68 publications

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

Repeated aripiprazole treatment causes dopamine D2 receptor up-regulation and dopamine supersensitivity in young rats

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

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