Altered emotional behaviors and the expression of 5-HT1A and M1 muscarinic receptors in micro-opioid receptor knockout mice

Anxiety and depression alterations have been reported in micro-opioid receptor knockout mice after exon 2 disruption. However, emotional behaviors, such as novelty and emergence responses have not been reported in micro-opioid receptor knockout mice due to the disruptions of exon 2 and 3. Here, we report that mu-opioid receptor knockout mice, with deletion of exon 2 and 3, display significant emotional behavior changes; they showed less anxiety in the elevated plus maze and emergence tests, reduced response to novel stimuli in the novelty test, and less depressive-like behavior in the forced-swim test. Analysis of the compensatory mechanism in mu-opioid receptor knockout mice revealed that the M1 mRNA levels were reduced in the cortex, caudate putamen, nucleus accumbens, and hippocampus, and that M1 receptor levels were reduced in the nucleus accumbens, CA1, and the dentate gyrus of the hippocampus, versus the wild-type. However, 5-HT1A receptor levels were significantly elevated in the cerebral cortex and in the hypothalamus of mu-opioid receptor knockout mice versus the wild-type. These aberrant emotional behavioral phenotypes are possibly related to M1 and 5-HT1A receptor alterations in the micro-opioid receptor knockout mice. Overall, our study suggests that micro-opioid receptor may play a role in the modification of emotional responses to novelty, anxiety, and depression.