TY - JOUR
T1 - Cortical endogenous opioids and their role in facilitating repetitive behaviors in deer mice
AU - Augustine, Farhan
AU - Rajendran, Shreenath
AU - Singer, Harvey S.
N1 - Funding Information:
We wish to thank Dr. Mary E. Blue for her expert guidance in stereological analysis, Dr. Senthil S. Karuppagounder for his assistance during the preliminary HPLC analysis and tissue dissections, and all the staff of Molecular Characterization and Analysis Complex (MCAC) at the University of Maryland Baltimore County (UMBC). This work was supported by philanthropic gifts to the Johns Hopkins Motor Stereotypy Research Initiative Fund from the Nesbitt-McMaster Foundation, Klump Family, and Graves Family.
Funding Information:
We wish to thank Dr. Mary E. Blue for her expert guidance in stereological analysis, Dr. Senthil S. Karuppagounder for his assistance during the preliminary HPLC analysis and tissue dissections, and all the staff of Molecular Characterization and Analysis Complex (MCAC) at the University of Maryland Baltimore County (UMBC) . This work was supported by philanthropic gifts to the Johns Hopkins Motor Stereotypy Research Initiative Fund from the Nesbitt-McMaster Foundation , Klump Family, and Graves Family.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/2/3
Y1 - 2020/2/3
N2 - Deer mice provide a non-pharmacologically induced model for the study of repetitive behaviors. In captivity, these animals develop frequent jumping and rearing that resemble clinical symptoms of obsessive-compulsive behavior (OCB), autism spectrum disorder (ASD), complex motor stereotypies (CMS), and Tourette's syndrome (TS). In this study, we pursue the mechanism of repetitive behaviors by performing stereological analyses and liquid chromatography/ mass spectrometry (LC–MS/MS) measurements of glutamate (Glut), GABA, 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), leu-enkephalin (leu-enk), and dynorphin-A (dyn-A) in frontal cortex (FC), prefrontal cortex (PFC), and basal ganglia. The only significant stereological alteration was a negative correlation between repetitive behaviors and the cell count in the ventromedial striatum (VMS). Neurochemical analyses demonstrated a significant negative correlation between repetitive behaviors and endogenous opioids (leu-enk and dyn-A) in the FC – the site of origin of habitual behaviors and cortical projections to striatal MSNs participating in direct and indirect pathways. The precise neurochemical process by which endogenous opioids influence synaptic neurotransmission is unknown. One postulated cortical mechanism, supported by our findings, is an opioid effect on cortical interneuron GABA release and a consequent effect on glutamatergic cortical pyramidal cells. Anatomical changes in the VMS could have a role in repetitive behaviors, recognizing that this region influences goal-directed and habitual behaviors.
AB - Deer mice provide a non-pharmacologically induced model for the study of repetitive behaviors. In captivity, these animals develop frequent jumping and rearing that resemble clinical symptoms of obsessive-compulsive behavior (OCB), autism spectrum disorder (ASD), complex motor stereotypies (CMS), and Tourette's syndrome (TS). In this study, we pursue the mechanism of repetitive behaviors by performing stereological analyses and liquid chromatography/ mass spectrometry (LC–MS/MS) measurements of glutamate (Glut), GABA, 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), leu-enkephalin (leu-enk), and dynorphin-A (dyn-A) in frontal cortex (FC), prefrontal cortex (PFC), and basal ganglia. The only significant stereological alteration was a negative correlation between repetitive behaviors and the cell count in the ventromedial striatum (VMS). Neurochemical analyses demonstrated a significant negative correlation between repetitive behaviors and endogenous opioids (leu-enk and dyn-A) in the FC – the site of origin of habitual behaviors and cortical projections to striatal MSNs participating in direct and indirect pathways. The precise neurochemical process by which endogenous opioids influence synaptic neurotransmission is unknown. One postulated cortical mechanism, supported by our findings, is an opioid effect on cortical interneuron GABA release and a consequent effect on glutamatergic cortical pyramidal cells. Anatomical changes in the VMS could have a role in repetitive behaviors, recognizing that this region influences goal-directed and habitual behaviors.
KW - Deer mice
KW - Direct and indirect pathways
KW - Endogenous opioids
KW - Goal-directed pathway
KW - Habitual pathway
KW - Neurotransmitters
KW - Repetitive behaviors
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U2 - 10.1016/j.bbr.2019.112317
DO - 10.1016/j.bbr.2019.112317
M3 - Article
C2 - 31676208
AN - SCOPUS:85076224837
SN - 0166-4328
VL - 379
JO - Behavioural Brain Research
JF - Behavioural Brain Research
M1 - 112317
ER -