AM 
VT 
NA 
NS 
CT 
' J§ 
Si 
- 
fl' 
m m <* — c-fos 
- + 
- + 
" + 
- + 
. + withdrawal 
v" ■ t • 
% |p; 
-4 C-fos 
PNS 
PGI 
HP 
DR 
PAG 
FIGURE 5. Autoradiograms showing regulation of Fos mRNA in various 
regions of rat brain in response to opiate withdrawal. Opiate 
withdrawal was precipitated in morphine-tolerant rats by SC 
administration of naltrexone. Animals were sacrificed 1 hour 
after the initiation of withdrawal, and levels of Fos mRNA were 
analyzed (using 5 to 10 mg of total RNA) by Northern blotting. 
AM, amygdala; VT, ventral tegmental area; NA, nucleus 
accumbens; NS, neostriatum (caudate/putamen); CT, whole 
cerebral cortex; PNS, whole cross-sections of anterior pons 
from which LC nuclei had been excised; PCI, nucleus 
paragigantocellularis; HP, hippocampus; DR, dorsal raphe; 
PAG, periaqueductal gray. 
SOURCE: Hayward et al. 1990. Copyright 1990 by Elsevier Science 
Publishers (Amsterdam). 
CREB in the LC, an effect that diminishes after chronic exposure to the 
opiate. In contrast, precipitation of opiate withdrawal increases CREB 
phosphorylation in this brain region (Guitart et al. 1992). This regulation 
of CREB phosphorylation is consistent with the known effects of acute and 
chronic opiates and opiate withdrawal on the activity of the cAMP system in 
the LC. 
These studies of opiate regulation of transcription factors, although preliminary, 
highlight the utility of the LC as a model system in which to study transcription 
factor regulation. The LC is a system in which specific candidate target genes 
have been identified and in which changes in those genes have been shown to 
106 
