Kappa Opioid Receptor Activation Disrupts Prepulse Inhibition of the Acoustic Startle in Rats

摘要: Background Compelling evidence indicates that kappa opioid receptor (KOR) agonists produce perceptual distortions in animals and humans, yet the mechanism of action clinical relevance such effects remain unclear. Since abnormalities preattentional functions informational processing are hypothesized to underlie psychotic disorders, present study has been designed assess role KOR on sensorimotor gating. Methods The selective agonist U50488 were evaluated behavioral paradigm prepulse inhibition (PPI) acoustic startle reflex (ASR). Results (1.25, 2.5, 5 mg/kg, subcutaneous [SC]) induced a dose-dependent reduction PPI, which was efficiently prevented by antagonist norbinaltorphimine (nor-BNI, 10 SC), as well atypical antipsychotic clozapine (5, 8 intraperitoneal [IP]) but not typical haloperidol (.1, .5 IP). Conversely, nor-BNI (10 SC) failed reverse PPI disruption mediated both apomorphine (.25 dizocilpine (.1 SC). Conclusions Our results support pivotal regulation gating, pointing these receptors possible neurobiological substrate especially relevant clusters psychosis unresponsive antipsychotics.