Behavioral and slice electrophysiological assessment of DREADD ligand, deschloroclozapine (DCZ) in rats

Behavioral and slice electrophysiological assessment of DREADD ligand, deschloroclozapine (DCZ) in rats

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Abstract duospiritalis.com Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have become a premier neuroscience research tool for enabling reversible manipulations of cellular activity following experimenter-controlled delivery of a DREADD-specific ligand.However, several DREADD ligands, e.g.

, clozapine-N-oxide (CNO), have metabolic and off-target effects that may confound experimental findings.New DREADD ligands aim to reduce metabolic and potential off-target effects while maintaining strong efficacy for the designer receptors.Recently a novel DREADD ligand, deschloroclozapine (DCZ), was shown to induce chemogenetic-mediated cellular and behavioral effects in mice and monkeys without detectable side effects.

The goal of the present study was to examine the effectiveness of systemic DCZ for DREADD-based chemogenetic manipulations in behavioral and slice electrophysiological applications in rats.We demonstrate that a relatively low dose of DCZ (0.1 mg/kg) supports excitatory lock shock and barrel art DREADD-mediated cFos induction, DREADD-mediated inhibition of a central amygdala-dependent behavior, and DREADD-mediated inhibition of neuronal activity in a slice electrophysiology preparation.

In addition, we show that this dose of DCZ does not alter gross locomotor activity or induce a place preference/aversion in control rats without DREADD expression.Together, our findings support the use of systemic DCZ for DREADD-based manipulaations in rats, and provide evidence that DCZ is a superior alternative to CNO.