Dataset Information

Estrous cycle influences cell-type-specific translatomic signatures of repeated ketamine exposure in the rat nucleus accumbens

ABSTRACT: The growing therapeutic promise of repeated, low-dose ketamine treatment across various psychopathologies-including depression and drug addiction-warrants clarity on its potential addictive properties and their associated mechanisms in both sexes. Accordingly, the present work examined the effects of repeated low-doses ketamine in male and female rats on behavioral sensitization to the locomotor activating effects of ketamine, as well as the associated molecular profiles in dopamine D1- and D2-receptor-expressing medium spiny neurons (D1- and D2-MSNs) of the nucleus accumbens (NAc). Following intra-NAc infusion of a Cre-inducible RiboTag virus, locomotor activity was measured in adult Drd1a-iCre and Drd2-iCre male and female rats in either diestrus or proestrus following repeated administration of ketamine (0, 10, or 20 mg/kg, i.p.) to evaluate the development of locomotor sensitization. Female-but not male-rats developed sensitization to the locomotor-activating effects of ketamine, occurring more rapidly in proestrus than in diestrus females at the lower dose tested. To examine enduring context- and cell-type-specific changes in translating mRNAs associated with sensitization to ketamine, RNA sequencing was performed on polyribosome-bound mRNA of D1- and D2-MSNs isolated from the NAc of sensitized females in a drug-free state. A greater number of differentially expressed genes were observed selectively in D1-MSNs of ketamine-treated proestrus compared to diestrus females, which were broadly related to regulation of transcription and epitranscriptional modification. These findings provide novel evidence of cell-type-specific and estrous-cycle-dependent molecular profiles responsive to intermittent ketamine treatment in female rats and identify post-transcriptional mechanisms with relevance to ketamine's effects on behavioral plasticity.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE303789 | GEO | 2026/01/27

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other
	GSE303789_ALL_raw_counts.txt.gz	Txt

Items per page:

1 - 2 of 2

Similar Datasets

Project description:The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9 positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSNs identity and repressing D1-MSNs identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2 like-MSNs survived normally in adulthood. Taken together, our finding supported that Sp9 was sufficient to promote D2-MSNs identity and repress D1-MSNs identity, and Sp9 was a negative regulator of D1-MSNs fate. The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9 positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSNs identity and repressing D1-MSNs identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2 like-MSNs survived normally in adulthood. Taken together, our finding supported that Sp9 was sufficient to promote D2-MSNs identity and repress D1-MSNs identity, and Sp9 was a negative regulator of D1-MSNs fate.

Dataset Information

Estrous cycle influences cell-type-specific translatomic signatures of repeated ketamine exposure in the rat nucleus accumbens

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets