Cocaine exposure during the early postnatal period diminishes medial frontal cortex Gs coupling to dopamine D1-like receptors in adult rat.
The effect of cocaine exposure during early postnatal ages on coupling of dopamine (DA) D(1)- and D(2)-like receptors to their respective Gs/olf and Gi was examined in striatum and medial frontal cortex (MFC). Sprague-Dawley rats were subcutaneously injected with either 50 mg/kg cocaine or vehicle during postnatal day (PnD) 11-20 and dopaminergic D(1)- and D(2)-like receptor signaling was evaluated at PnD 60. Results showed that cocaine exposure did not affect the magnitude of both DA D(1)- and D(2)-like receptor coupling to their respective Gs/olf and Gi in striatum. However, in the medial frontal cortex, the basal and the DA D(1)-like receptor and Gs association were reduced in cocaine-exposed brains. However, there was no change in basal or DA D(2)-like receptor-Gi linkage in medial frontal cortex. Since frontal cortex plays a critical role in regulating cognition and working memory, disruption of DA-modulated circuits or alteration of dopaminergic activity resulting from postnatal cocaine exposure may result in abnormal responses to environmental challenges leading to long-term behavioral changes.
Zhao
Ning
N
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, United States.
Wang
Hoau-Yan
HY
Dow-Edwards
Diana
D
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D001523:Mental Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013995:Time
D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D003042:Cocaine; D004298:Dopamine