Alterations in the level of OFQ/N-IR in rat brain regions by cocaine

Abstract

We have previously shown that administration of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, into the lateral ventricles or VTA blocked cocaine sensitization. In the present study, we determined the effect of acute and chronic cocaine treatment on the level of endogenous OFQ/N in rat brain regions. Male Sprague Dawley rats were tested for motor activity in response to saline or cocaine (20 mg/kg) injection once daily for three consecutive days. To determine the effect of single or repeated cocaine administration on the level of OFQ/N, rats were sacrificed one hour following saline or cocaine injection either on day 1 or 3, respectively. Additional groups of rats were treated similarly with saline or cocaine on days 1-3 and sacrificed or tested for locomotor sensitization on day 8. Consistent with previous studies, repeated cocaine administration induced locomotor sensitization to a challenge dose of cocaine (7.5 mg/kg) given on day 8. Measurements of tissue content of OFQ/N-IR using radioimmunoassay indicated that the rat hypothalamus and striatum respectively contained the highest and lowest level of the peptide among the brain regions tested. Acute cocaine decreased the level of OFQ-IR in the rat midbrain and to a lesser extent in the striatum. On the other hand, the level of OFQ/N was higher in rats treated with cocaine on days 1-3 and sacrificed on day 8. These findings suggest that endogenous OFQ/N may be involved in the actions of cocaine and possibly in cocaine-induced motor stimulation and locomotor sensitization.

Orphanin FQ/Nociceptin Not Only Blocks but Also Reverses Behavioral Adaptive Changes Induced by Repeated Cocaine in Mice

“…These intriguing results imply that neuronal adaptive changes may occur along the OFQ/N/ORL-1 receptor system following repeated cocaine treatment. Consistent with this notion, we have previously shown that the level of OFQ/N was increased in the hippocampus of rats sensitized to cocaine (45). Thus, further research is needed to elucidate the underlying mechanisms of these neuronal and behavioral adaptive changes in the OFQ/N/ORL-1 receptor system following repeated cocaine treatment.…”

The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction

“…Interestingly, however, the level of OFQ/N-IR was found to be increased in the hippocampus of rats that received repeated intermittent cocaine treatment and showed locomotor sensitization. 71 These results suggest that the endogenous OFQ/N may be involved in the acute and chronic actions of cocaine.…”

“…Reductions were also seen in the striatum and prefrontal cortex but these changes were not significantly different from the saline-treated controls. 71 However, tissue content does not provide information about the release, metabolism, and/or synthesis of the peptide. Additionally, given that these changes were measured 1 h after cocaine administration, future studies using microdialysis in freely moving animals are needed to assess the dose–-response and time course effect of single and repeated cocaine administration on the release of endogenous OFQ/N.…”

Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin

“…For example, acute ethanol administration increases NOP receptor density in cortical areas, whereas acute administration of cocaine does not (Rosin et al, 2003). Furthermore, under chronic treatment conditions, alcohol administration decreases N/OFQ brain tissue levels (Lindholm et al, 2002), whereas repeated cocaine administration increases N/OFQ immunoreactivity in the brain (Lutfy et al, 2008). …”