Original articleKappa Opioid Receptor Activation Disrupts Prepulse Inhibition of the Acoustic Startle in Rats
Section snippets
Animals
Two hundred seventy-eight male Sprague-Dawley albino rats (Harlan, Italy) weighing between 200 g and 300 g served as subjects in the present study. Rats were housed four per cage in the animal care quarters, maintained at a temperature of 22 ± 2°C on a reversed 12-hour light-dark cycle (lights went off at 7 am and on at 7 pm). Food and water were available ad libitum, and each rat was handled for 5 minutes on each of the 5 days prior to experiment to minimize stress effects. All experimental
Results
Throughout the study, no-stimulus trials data were found negligible in comparison with other startle values and nor were they affected by any drug treatment; therefore, they will not be presented here.
Discussion
The present study has shown that the administration of the potent KOR agonist U50488 induces a significant, dose-dependent reduction of PPI in rats. This effect was fully reversed by a pretreatment with the selective KOR antagonist nor-BNI, providing compelling evidence that stimulation of KOR disrupts sensorimotor gating. This result supports and complements the clinical evidence that KOR are involved in the pathophysiology of hallucinatory disorders (Pfeiffer et al 1986: Roth et al 2002:
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Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?
2020, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Impairments in cortically mediated tasks are observed following opioid system modulation in rodents. Impaired pre-pulse inhibition of acoustic startle following systemic administration of KOR agonists indicates a role for opioid signaling in preattentional information processing (Bortolato et al., 2005). In addition, systemic KOR or MOR agonists increase distractibility and impair performance during a five-choice serial reaction time task that assesses attentional capacity and impulsive behavior (Maguire et al., 2016; Shannon et al., 2007).
Opioid modulation of cognitive impairment in depression
2018, Progress in Brain ResearchCitation Excerpt :Similarly, no inhibition of PPI was evident in rats and mice treated systemically with the nonselective opioid receptor antagonist naloxone (Swerdlow et al., 1991), the selective MOR antagonist naloxonazine (35 g/kg) (Ukai and Okuda, 2003), and centrally with the MOR antagonist β-FNA (5 μg) (Ukai and Okuda, 2003). Neither did the selective KOR antagonists CERC-501 (3, 10, or 30 mg/kg) and nor-BNI (10 mg/kg) (Bortolato et al., 2005; Halberstadt et al., 2016; Rorick-Kehn et al., 2014; Tejeda et al., 2010) reduce PPI when administered alone. However, low-dose naltrexone (0.03, 0.1, or 0.3 mg/kg) attenuated morphine-induced PPI reductions (Rorick-Kehn et al., 2014), whereas the selective KOR antagonist CERC-501 (10 or 30 mg/kg) did not attenuate morphine-induced reduction of PPI (Rorick-Kehn et al., 2014).
Effects of the psychotomimetic benzomorphan N-allylnormetazocine (SKF 10,047) on prepulse inhibition of startle in mice
2016, Pharmacology Biochemistry and BehaviorLY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders
2014, NeuropharmacologyCitation Excerpt :Although deficits in PPI are often used in preclinical models and clinical assessment of schizophrenia, PPI dysfunction occurs in other psychiatric and neurological disorders involving deficits of attention (Braff et al., 2001). Kappa and mu receptor agonists have been demonstrated to disrupt cognition in humans (Kamboj et al., 2005; Pfeiffer et al., 1986) and can disrupt PPI in rodents (Bortolato et al., 2005; Meng et al., 2010; but see Tejeda et al., 2010). We tested LY2456302 for its effects on PPI alone and for its ability to reverse PPI deficits induced by U-69593 and morphine.
Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the κ opioid agonist Salvinorin A in humans
2012, Biological PsychiatryCitation Excerpt :Salvinorin A induces psychosis-like effects but decreases DA in several brain regions (43,44), which arguably was indirectly reflected in the increased prolactin levels observed in this study. Furthermore, the DA D2 receptor antagonist haloperidol does not attenuate the deficits in prepulse inhibition produced by KOR activation (88). The only known mechanism of action of SA is KOR agonism.