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Enhancement of spatial attention in nociceptin/orphanin FQ receptor-knockout mice
1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan.
Abstract:
We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-knockout mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-knockout mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-knockout mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic-acid-induced writhing tests compared to those of wild-type mice. The nociceptin receptor-knockout mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-knockout mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-knockout mice than wild-type mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.
Insights
Mice lacking the nociceptin receptor showed no changes in pain sensitivity but demonstrated enhanced spatial attention. This suggests the nociceptin receptor regulates attention via the brain's dopamine system.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The nociceptin system, involving the nociceptin receptor (MOR-C), is implicated in auditory system regulation.
- Nociceptin receptor-knockout mice have been generated, but their behavioral characteristics require further investigation.
Purpose of the Study:
- To characterize the behavioral performances of nociceptin receptor-knockout mice.
- To investigate the role of the nociceptin receptor in pain perception, anxiety, and spatial learning.
- To explore the neurochemical underpinnings of observed behavioral changes.
Main Methods:
- Generation and behavioral testing of nociceptin receptor-knockout mice.
- Assessment of nociceptive thresholds using hot-plate, electric foot-shock, tail-flick, and acetic acid-induced writhing tests.
- Evaluation of anxiety-like behavior using the elevated plus-maze task.
- Measurement of spatial learning and attention using the water-finding test.
- Biochemical analysis of dopamine content in the frontal cortex.
Main Results:
- Nociceptin receptor-knockout mice exhibited unchanged nociceptive thresholds across multiple pain tests.
- No significant behavioral alterations were observed in the elevated plus-maze task.
- Surprisingly, knockout mice displayed enhanced retention of spatial attention (latent learning) in the water-finding test.
- Dopamine levels in the frontal cortex were reduced in knockout mice compared to wild-type controls.
Conclusions:
- The nociceptin receptor is not essential for regulating pain perception or anxiety-like behaviors.
- The nociceptin receptor plays a crucial role in spatial attention and latent learning.
- These effects are likely mediated through the regulation of the dopaminergic system in the brain.