Altered emotional behaviors and the expression of 5-HT_1A and M₁ muscarinic receptors in μ-opioid receptor knockout mice

Anxiety and depression alterations have been reported in μ-opioid receptor knockout mice after exon 2 disruption. However, emotional behaviors, such as novelty and emergence responses have not been reported in μ-opioid receptor knockout mice due to the disruptions of exon 2 and 3. Here, we report that μ-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 μ-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-HT_1A receptor levels were significantly elevated in the cerebral cortex and in the hypothalamus of μ-opioid receptor knockout mice versus the wild-type. These aberrant emotional behavioral phenotypes are possibly related to M₁ and 5-HT_1A receptor alterations in the μ-opioid receptor knockout mice. Overall, our study suggests that μ-opioid receptor may play a role in the modification of emotional responses to novelty, anxiety, and depression.