PMID- 34291671
OWN - NLM
STAT- MEDLINE
DCOM- 20220209
LR  - 20220716
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 35
IP  - 10
DP  - 2021 Oct
TI  - Transgenerational evidence of increases in dopamine D2 receptor sensitivity in 
      rodents: Impact on sensorimotor gating, the behavioral response to nicotine and 
      BDNF.
PG  - 1188-1203
LID - 10.1177/02698811211033927 [doi]
AB  - BACKGROUND/AIMS: Neonatal quinpirole (NQ) treatment to rats increases dopamine 
      D(2) (DAD(2)) receptor sensitivity in adult animals. We investigated if increased 
      DAD(2) sensitivity would be passed to the next (F1) generation, and if these 
      animals demonstrated sensorimotor gating deficits and enhanced behavioral 
      responses to nicotine. METHODS: Male and female rats were intraperitoneal (IP) 
      administered quinpirole (1 mg/kg) or saline (NS) from postnatal day (P)1-21. 
      Animals were either behaviorally tested (F0) or raised to P60 and mated, creating 
      F1 offspring. RESULTS: Experiment 1 revealed that F1 generation animals that were 
      the offspring of at least one NQ-treated founder increased yawning behavior, a 
      DAD(2)-mediated behavioral event, in response to acute quinpirole (0.1 mg/kg). F1 
      generation rats also demonstrated increased striatal beta arrestin-2 and decreased 
      phospho-AKT signaling, consistent with increased G-protein independent DAD(2) 
      signaling, which was equal to F0 NQ-treated founders, although this was not 
      observed in all groups. RNA-Seq analysis revealed significant gene expression 
      changes in the F1 generation that were offspring of both NQ-treated founders 
      compared to F0 NQ founders and controls, with enrichment in sensitivity to stress 
      hormones and cell signaling pathways. In Experiment 2, all F1 generation 
      offspring demonstrated sensorimotor gating deficits compared to controls, which 
      were equivalent to F0 NQ-treated founders. In Experiment 3, all F1 generation 
      animals demonstrated enhanced nicotine behavioral sensitization and nucleus 
      accumbens (NAcc) brain-derived neurotrophic factor (BDNF) protein. Further, F1 
      generation rats demonstrated enhanced adolescent nicotine conditioned place 
      preference equivalent to NQ-treated founders conditioned with nicotine. 
      CONCLUSIONS: This represents the first demonstration of transgenerational effects 
      of increased DAD(2) sensitivity in a rodent model.
FAU - Gill, Wesley Drew
AU  - Gill WD
AD  - James H. Quillen College of Medicine, East Tennessee State University, Johnson 
      City, TN, USA.
FAU - Burgess, Katherine C
AU  - Burgess KC
AD  - James H. Quillen College of Medicine, East Tennessee State University, Johnson 
      City, TN, USA.
FAU - Vied, Cynthia
AU  - Vied C
AD  - Translational Science Laboratory, Florida State University College of Medicine, 
      Tallahassee, FL, USA.
FAU - Brown, Russell W
AU  - Brown RW
AUID- ORCID: 0000-0002-6512-7315
AD  - James H. Quillen College of Medicine, East Tennessee State University, Johnson 
      City, TN, USA.
LA  - eng
GR  - C06 RR030651/RR/NCRR NIH HHS/United States
GR  - R15 DA046926/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20210722
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DRD2 protein, rat)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Receptors, Dopamine D2)
RN  - 20OP60125T (Quinpirole)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dopamine Agonists/pharmacology
MH  - Female
MH  - Male
MH  - Nicotine/*pharmacology
MH  - Nucleus Accumbens/drug effects
MH  - Quinpirole/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/*metabolism
MH  - Sensory Gating/*drug effects
PMC - PMC9169618
MID - NIHMS1738103
OTO - NOTNLM
OT  - Epigenetic
OT  - behavioral sensitization
OT  - brain-derived neurotrophic factor
OT  - conditioned place preference
OT  - dopamine D2 receptor
OT  - nicotine
OT  - quinpirole
EDAT- 2021/07/23 06:00
MHDA- 2022/02/10 06:00
PMCR- 2022/06/06
CRDT- 2021/07/22 08:38
PHST- 2021/07/23 06:00 [pubmed]
PHST- 2022/02/10 06:00 [medline]
PHST- 2021/07/22 08:38 [entrez]
PHST- 2022/06/06 00:00 [pmc-release]
AID - 10.1177/02698811211033927 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2021 Oct;35(10):1188-1203. doi: 10.1177/02698811211033927. 
      Epub 2021 Jul 22.