Effects of nociceptin/orphanin FQ in the acquisition of contextual and tone fear conditioning in rats.

Abstract

Nociceptin, or orphanin FQ (N/OFQ), the endogenous ligand of NOP receptors, is known to regulate learning and memory processes. To verify the role of N/OFQ in the acquisition of contextual (CFC) and tone fear conditioning (TFC), Wistar male rats received intracerebroventricular injections of N/OFQ (0.1-5.0 nmol) before training, and were tested 24 and 48 hr later to access the freezing response to context and tone, respectively. The intermediate doses (1.0 and 2.5 nmol) impaired the CFC test, sparing TFC. The highest dose (5.0 nmol) reduced freezing during both tests, a result that may be due to nonspecific effects. The posttraining injection of N/OFQ (1 or 5 nmol) did not interfere with CFC and TFC, suggesting a specific effect of the peptide in acquisition processes. Moreover, the impairment observed with N/OFQ (1 nmol) in CFC cannot be attributed to a state-dependent learning because it was not reversed by its pretest administration. The data support the negative role of N/OFQ in the acquisition of aversively motivated tasks, which encompass a spatial component and depend on the hippocampus.

Nociceptin/orphanin FQ induces simultaneously anxiolytic and amnesic effects in the mouse elevated T-maze task

“…Few studies investigated the effects of N/OFQ posttraining injected. Similar to our findings, N/OFQ (1 or 5 nmol) injected in the lateral ventricle did not interfere with acquisition of contextual and tone fear conditioning when posttraining injected, suggesting a specific effect of the peptide in acquisition processes (Fornari et al 2008). However, microinjection of N/OFQ (1-100 pmol) into the basolateral amygdala of rats immediately after inhibitory avoidance training induced dose-and time-dependent impairment of 48-h inhibitory avoidance retention performance, which was blockaded by a NOP antagonist (Roozendaal et al 2007).…”

Endogenous Nociceptin System Involvement in Stress Responses and Anxiety Behavior

“…Most recently intracerebroventricular (i.c.v.) injection of N/OFQ has been shown to dose-relatedly impair the acquisition of contextual and tone fear conditioning in rats (Fornari, Soares, Ferreira, Moreira, & Oliveira, 2008). Low-moderate (0.1-2.5 nmol i.c.v.)…”

Nociceptin and the nociceptin receptor in learning and memory

“…NOP receptor agonism with N/OFQ or the NOP receptor agonist Ro64-6198 has consistently been shown to impair memory consolidation in contextual fear and passive avoidance paradigms (Fornari et al, 2008; Goeldner et al, 2009; Higgins et al, 2002; Hiramatsu and Inoue, 1999; Mamiya et al, 2003; Roozendaal et al, 2007), tasks highly dependent on hippocampal functioning. However, results in cued-fear conditioning, where the association of the CS+US is dependent primarily on the amygdala, appear to be drug and dose dependent.…”