The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus.
We have previously shown that a membrane-permeant analog of cAMP, 8-bromo-cAMP (8-br-cAMP), elicits a vigorous eating response when microinjected into the perifornical hypothalamus (PFH) or lateral hypothalamus (LH) of satiated rats, suggesting that increases in cAMP in these areas may be important in the neural control of eating. To determine the locus of this effect, we compared the ability of 8-br-cAMP (1-100 nmol/0.3 microl) to elicit eating after microinjection into the PFH, LH, or the following bracketing areas: the anterior and posterior LH, paraventricular nucleus of the hypothalamus, thalamus, and amygdala. 8-br-cAMP at 50 nmol elicited eating (>/=3.4 gm in 2 hr) exclusively in the PFH and LH. At 100 nmol, 8-br-cAMP elicited a larger response in these areas and elicited a smaller, more variable response in the thalamus. We similarly mapped the feeding-stimulatory effects of compounds that increase endogenous cellular cAMP in naive rats. Combined microinjection of matched doses (300 nmol) of 3-isobutyl-1-methylxanthine and 7-deacetyl-7-O-(N-methylpiperazino)-gamma-butyryl-forskolin was effective exclusively in the PFH, eliciting an average 2 hr food intake of 8.4 +/- 2.0 gm. Collectively, these results suggest that increases in cellular cAMP within a specific brain site, the PFH, may play a role in the neural stimulation of eating.
Gillard
E R
ER
Department of Neuroscience, University of California at Riverside, Riverside, California 92521, USA.
Khan
A M
AM
Grewal
R S
RS
Mouradi
B
B
Wolfsohn
S D
SD
Stanley
B G
BG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D004224:Diterpenes; D004435:Eating / Q000187:drug effects*; D007026:Hypothalamic Area, Lateral / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology*
D004224:Diterpenes; D010726:Phosphodiesterase Inhibitors; C055627:L 858051; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015056:1-Methyl-3-isobutylxanthine