Inhibition of 5[alpha]-reductase attenuates behavioral effects of D1-, but not D2-like receptor agonists in C57BL/6 mice

• Published in: Psychoneuroendocrinology Vol. 38; no. 4; pp. 542 - 551
• Main Authors: Frau, Roberto, Pillolla, Giuliano, Bini, Valentina, Tambaro, Simone, Devoto, Paola, Bortolato, Marco
• Format: Journal Article
• Language: English
• Published: 01.04.2013
• Subjects: Acoustic startle response; Apomorphine; Channel gating; Data processing; Dopamine D1 receptors; Dopamine D2 receptors; Dopamine receptors; Enzymes; Neurosteroidogenesis; Neurosteroids; Neurotransmission; quinpirole; Reflexes; Sensorimotor gating; Startle response; Steroid hormones
• ISSN: 0306-4530

Converging lines of evidence point to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of steroid 5[alpha]-reductase (5[alpha]R), the key rate-limiting enzyme in neurosteroidogenesis, attenuates the behavioral effects of non-selective DA receptor agonists in rats, including stereotyped responses and sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. Since previous findings suggested that the role of DA D1- and D2-like receptor families in behavioral regulation may exhibit broad interspecies and interstrain variations, we assessed the impact of 5[alpha]R blockade on the behavioral effects of DAergic agonists in C57BL/6 mice. The prototypical 5[alpha]R inhibitor finasteride (FIN; 25a50 mg/kg, intraperitoneally, IP) dose-dependently countered the PPI deficits and the enhancement of rearing responses induced by the full D1-like receptor agonist SKF-82958 (0.3 mg/kg, IP); however, FIN did not significantly affect the hyperlocomotive and startle-attenuating effects of SKF-82958. Whereas the D2-like receptor agonist quinpirole (QUIN; 0.5 mg/kg, IP) did not induce significant changes in PPI, the combination of this agent and FIN surprisingly produced marked gating and startle deficits. In contrast with previous data on rats, FIN did not affect the reductions of startle reflex and PPI produced by the non-selective DAergic agonist apomorphine (APO; 0.5 mg/kg, IP). These findings collectively indicate that, in C57BL/6 mice, 5[alpha]R differentially modulates the effects of D1- and D2-like receptor agonists in behavioral regulation.