Eating induced by perifornical cAMP is behaviorally selective and involves protein kinase activity.
It has previously been shown that agents that increase endogenous cAMP elicit robust eating when injected into the perifornical hypothalamus (PFH) but not when injected into surrounding brain sites, suggesting that PFH cAMP may play a role in eating control. We report here that bilateral microinjection of the adenylyl cyclase activator 7-deacetyl-7-O-(N-methylpiperazino)-gamma-butyryl-forskolin dihydrochloride (MPB forskolin; 300 nmol/0.3 microl) into the PFH is sufficient to elicit intense eating (up to 15.7 +/- 2.3 g in 2 h) in satiated rats, without concomitant effects on other behaviors, including gnawing and drinking. In contrast, the inactive analog 1, 9-dideoxyforskolin is ineffective, suggesting that the effects of MPB forskolin are behaviorally selective and pharmacologically specific. We also show that injection of the protein kinase A inhibitor H-89 (100 nmol) into the PFH reduced MPB forskolin-induced eating by up to 50%. Collectively, these results suggest that increased cAMP production in a single brain area may be sufficient to selectively generate a patterned, goal-oriented behavior by activating cAMP-dependent protein kinase.
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G OK6.
E R
ER
Gillard
A M
AM
Khan
B
B
Mouradi
O
O
Nalamwar
B G
BG
Stanley
D000262:Adenylyl Cyclases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004224:Diterpenes; D004327:Drinking Behavior / Q000187:drug effects; D004789:Enzyme Activation; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D006120:Grooming; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008409:Mastication; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects
D004224:Diterpenes; C055627:L 858051; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases