Altered prelimbic cortex output during cue-elicited drug seeking.
Cocaine treatment paired with environmental cues establishes a conditioned place preference (CPP) for that environment. After expression of this preference, rats show elevated levels of immediate early genes (IEGs; e.g. c-fos) in the prelimbic cortex (PrL), basolateral amygdala complex (BLC), and nucleus accumbens core (NAcc) compared with drug-unpaired controls. These findings, together with the known connections between these regions, suggest that they function as a circuit contributing to cue-elicited craving. To investigate the function of this circuit during drug-seeking, we characterized Fos immunoreactivity of particular neuron classes in each region. To distinguish between IEG activation of GABAergic and non-GABAergic (principally, excitatory projection) neurons, we combined Fos immunohistochemistry with immunohistochemistry for glutamic acid decarboxylase 67 (GAD67) or calcium/calmodulin-dependent protein kinase II (CAMKII) proteins. Within the BLC and NAcc of drug-paired and drug-unpaired animals tested for CPP, we observed no significant differences in the percentage of Fos-immunoreactive (IR) cells that were also GAD67-IR. We also observed no group difference in the degree of Fos/CAMKII overlap in the BLC. However, in PrL, the degree of Fos/GAD67 overlap in the drug-paired group was significantly higher than in the drug-unpaired group. Also, the Fos/CAMKII overlap in the entire PrL as well as just its layer V was significantly lower in the drug-paired animals compared with controls. These findings suggest that, during CPP expression in cocaine-paired animals, the PrL GABAergic interneurons are preferentially activated while PrL output is attenuated, perhaps through greater inhibition of layer V pyramidal neurons. These results suggest a shifting prefrontal cortex cell population response during cocaine-seeking.
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
Courtney A
CA
Miller
John F
JF
Marshall
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003463:Cues; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1