TY - JOUR
T1 - μ-opioid receptor (oprm1) copy number influences nucleus accumbens microcircuitry and reciprocal social behaviors
AU - Toddes, Carlee
AU - Lefevre, Emilia M.
AU - Brandner, Dieter D.
AU - Zugschwert, Lauryn
AU - Rothwell, Patrick E.
N1 - Publisher Copyright:
© 2021 Society for Neuroscience. All rights reserved.
PY - 2021/9/22
Y1 - 2021/9/22
N2 - The μ-opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in male and female mice with heterozygous genetic knockout of the μ-opioid receptor (Oprm11/2). This genetic condition models the partial reduction of μ-opioid receptor signaling reported in several neuropsychiatric disorders. We first analyzed inhibitory synapses in the nucleus accumbens, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the expression of gephyrin mRNA and the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in mutants of both sexes. Some of these changes were more robust in Oprm11/2 mutants than Oprm1-/- mutants, demonstrating that partial reductions of μ-opioid signaling can have large effects. At the behavioral level, social conditioned place preference and reciprocal social interaction were diminished in Oprm11/2 and Oprm1-/- mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of wild-type test partners. We corroborated this latter result using a social preference task, in which wild-type mice preferred interactions with another typical mouse over Oprm1 mutants. Surprisingly, Oprm1-/- mice preferred interactions with other Oprm1-/- mutants, although these interactions did not produce a conditioned place preference. Our results support a role for partial dysregulation of μ-opioid signaling in social deficits associated with neuropsychiatric conditions.
AB - The μ-opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in male and female mice with heterozygous genetic knockout of the μ-opioid receptor (Oprm11/2). This genetic condition models the partial reduction of μ-opioid receptor signaling reported in several neuropsychiatric disorders. We first analyzed inhibitory synapses in the nucleus accumbens, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the expression of gephyrin mRNA and the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in mutants of both sexes. Some of these changes were more robust in Oprm11/2 mutants than Oprm1-/- mutants, demonstrating that partial reductions of μ-opioid signaling can have large effects. At the behavioral level, social conditioned place preference and reciprocal social interaction were diminished in Oprm11/2 and Oprm1-/- mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of wild-type test partners. We corroborated this latter result using a social preference task, in which wild-type mice preferred interactions with another typical mouse over Oprm1 mutants. Surprisingly, Oprm1-/- mice preferred interactions with other Oprm1-/- mutants, although these interactions did not produce a conditioned place preference. Our results support a role for partial dysregulation of μ-opioid signaling in social deficits associated with neuropsychiatric conditions.
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U2 - 10.1523/JNEUROSCI.2440-20.2021
DO - 10.1523/JNEUROSCI.2440-20.2021
M3 - Article
C2 - 34301826
AN - SCOPUS:85115763644
SN - 0270-6474
VL - 41
SP - 7965
EP - 7977
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 38
ER -