PMID- 37922841
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1573-2509 (Electronic)
IS  - 0920-9964 (Linking)
VI  - 262
DP  - 2023 Dec
TI  - Sex-dependent emergence of prepubertal social dysfunction and augmented dopamine 
      activity in a neurodevelopmental rodent model relevant for schizophrenia.
PG  - 32-39
LID - S0920-9964(23)00398-5 [pii]
LID - 10.1016/j.schres.2023.10.036 [doi]
AB  - Schizophrenia is a neurodevelopmental psychiatric disorder that often emerges in 
      adolescence, is characterized by social dysfunction, and has an earlier onset in 
      men. These features have been replicated in rats exposed to the mitotoxin 
      methylazoxymethanol acetate (MAM) on gestational day (GD) 17, which as adults 
      exhibit behavioral impairments and dopamine (DA) system changes consistent with a 
      schizophrenia-relevant rodent model. In humans, social withdrawal is a negative 
      symptom that often precedes disease onset and DA system dysfunction and is more 
      pronounced in men. Children and adolescents at high-risk for schizophrenia 
      exhibit social deficits prior to psychotic symptoms (i.e., prodromal phase), 
      which can be used as a predictive marker for future psychopathology. Adult MAM 
      rats also exhibit deficient social interaction, but less is known regarding the 
      emergence of social dysfunction in this model, whether it varies by sex, and 
      whether it is linked to disrupted DA function. To this end, we characterized the 
      ontogeny of social and DA dysfunction in male and female MAM rats during the 
      prepubertal period (postnatal days 33-43) and found sex-specific changes in 
      motivated social behaviors (play, approach) and DA function. Male MAM rats 
      exhibited reduced social approach and increased VTA DA neuron activity compared 
      to saline-treated (SAL) males, whereas female MAM rats exhibited enhanced play 
      behaviors compared to SAL females but no changes in social approach or VTA 
      population activity during this period. These findings demonstrate sex 
      differences in the emergence of social and DA deficits in the MAM model, in which 
      females exhibit delayed emergence.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Rincon-Cortes, Millie
AU  - Rincon-Cortes M
AD  - Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, 
      Pittsburgh, PA 15260, United States. Electronic address: 
      millie.rincon-cortes@utdallas.edu.
FAU - Grace, Anthony A
AU  - Grace AA
AD  - Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, 
      Pittsburgh, PA 15260, United States.
LA  - eng
PT  - Journal Article
DEP - 20231101
PL  - Netherlands
TA  - Schizophr Res
JT  - Schizophrenia research
JID - 8804207
RN  - VTD58H1Z2X (Dopamine)
RN  - 592-62-1 (Methylazoxymethanol Acetate)
SB  - IM
MH  - Humans
MH  - Adolescent
MH  - Child
MH  - Rats
MH  - Male
MH  - Female
MH  - Animals
MH  - *Dopamine/physiology
MH  - *Schizophrenia/chemically induced
MH  - Rodentia
MH  - Methylazoxymethanol Acetate/toxicity
MH  - Neurons
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Development
OT  - Dopamine
OT  - MAM model
OT  - Schizophrenia
OT  - Sex differences
OT  - Social behavior
COIS- Declaration of competing interest MRC has no competing financial interests. AAG 
      received funds from the following organizations: Newron, Merck, SynAgile, 
      Alkermes, Lundbeck, Takeda, Roche, and Lyra.
EDAT- 2023/11/06 03:54
MHDA- 2023/12/17 09:42
CRDT- 2023/11/03 19:17
PHST- 2023/06/15 00:00 [received]
PHST- 2023/09/25 00:00 [revised]
PHST- 2023/10/28 00:00 [accepted]
PHST- 2023/12/17 09:42 [medline]
PHST- 2023/11/06 03:54 [pubmed]
PHST- 2023/11/03 19:17 [entrez]
AID - S0920-9964(23)00398-5 [pii]
AID - 10.1016/j.schres.2023.10.036 [doi]
PST - ppublish
SO  - Schizophr Res. 2023 Dec;262:32-39. doi: 10.1016/j.schres.2023.10.036. Epub 2023 
      Nov 1.