Behavioral and slice electrophysiological assessment of DREADD ligand, deschloroclozapine (DCZ) in rats.
Sci Rep
; 12(1): 6595, 2022 04 21.
Article
em En
| MEDLINE
| ID: mdl-35449195
ABSTRACT
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 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Drogas Desenhadas
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2022
Tipo de documento:
Article