Progress in neuro-psychopharmacology & biological psychiatry
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2018
ReviewZebrafish models relevant to studying central opioid and endocannabinoid systems.
The endocannabinoid and opioid systems are two interplaying neurotransmitter systems that modulate drug abuse, anxiety, pain, cognition, neurogenesis and immune activity. Although they are involved in such critical functions, our understanding of endocannabinoid and opioid physiology remains limited, necessitating further studies, novel models and new model organisms in this field. ⋯ Here, we discuss current models used to target the endocannabinoid and opioid systems in zebrafish, and their potential use in future translational research and high-throughput drug screening. Emphasizing the high degree of conservation of the endocannabinoid and opioid systems in zebrafish and mammals, we suggest zebrafish as an excellent model organism to study these systems and to search for the new drugs and therapies targeting their evolutionarily conserved mechanisms.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2018
Effects of alpha-7 nicotinic allosteric modulator PNU 120596 on depressive-like behavior after lipopolysaccharide administration in mice.
Evidence suggests that α7 nicotinic acetylcholine receptor (α7 nAChR) in the central nervous system has a critical role in the regulation of microglial function and neuroinflammation associated with the pathophysiology of major depressive disorder. The objectives of the present study were to determine the effects of PNU 120596, an α7 nAChR positive allosteric modulator (PAM), on depressive-like behavior and expression of ionized calcium binding adaptor molecule 1 (Iba-1), a microglial marker, in male C57BL/6J mice following lipopolysaccharide (LPS) administration, an animal model for depressive-like behavior. Forced swim test (FST), tail suspension test (TST), and sucrose preference test were used to determine the effects of PNU 120596 on depressive-like behavior, measured by increased immobility time or decreased sucrose preference. ⋯ Similarly, the PNU 120596 (4 mg/kg, i.p.) significantly reduced LPS-induced increased expression of Iba-1 in the hippocampus or prefrontal cortex. Overall, these results suggest that PNU 120596 reduces LPS-induced depressive-like behavior and microglial activation in the hippocampus and prefrontal cortex in mice. Therefore, α7 nAChR PAMs could be developed as potential therapeutic utility for the treatment of major depressive disorder in humans.