Characterization of behavioral changes in T-maze alternation from dopamine D₁ agonists with different receptor coupling mechanisms.

ABSTRACT:

Rationale

Dopamine D₁ receptor agonists have been shown to improve working memory, but often have a non-monotonic (inverted-U) dose-response curve. One hypothesis is that this may reflect dose-dependent differential engagement of D₁ signaling pathways, a mechanism termed functional selectivity or signaling bias.

Objectives and methods

To test this hypothesis, we compared two D₁ ligands with different signaling biases in a rodent T-maze alternation task. Both tested ligands (2-methyldihydrexidine and CY208243) have high intrinsic activity at cAMP signaling, but the former also has markedly higher intrinsic activity at D₁-mediated recruitment of β-arrestin. The spatial working memory was assessed via the alternation behavior in the T

SUBMITTER: Cimino JX 

PROVIDER: S-EPMC10693963 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature