Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats.
Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.
Intramural Research Program, NIDA/NIH, Baltimore, Maryland 21224, USA.
Carlo
C
Cifani
Eisuke
E
Koya
Brittany M
BM
Navarre
Donna J
DJ
Calu
Michael H
MH
Baumann
Nathan J
NJ
Marchant
Qing-Rong
QR
Liu
Thi
T
Khuc
James
J
Pickel
Carl R
CR
Lupica
Yavin
Y
Shaham
Bruce T
BT
Hope
D000818:Animals; D003345:Corticosterone / Q000097:blood; D055724:Electrophysiological Phenomena; D030762:Estrous Cycle / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D009474:Neurons / Q000502:physiology*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D013315:Stress, Psychological / Q000523:psychology*; D013565:Sympatholytics / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D013565:Sympatholytics; D049452:Green Fluorescent Proteins; D015016:Yohimbine; D003345:Corticosterone