title: Stimulation of eating by the second messenger cAMP in the perifornical and lateral hypothalamus.
abstract: Despite intense study of neurotransmitters mediating hypothalamic controls of food intake, little is known about which second messengers are critical for these mechanisms. To determine whether adenosine 3',5'-cyclic monophosphate (cAMP) might participate in these mechanisms, we injected the membrane-permeant cAMP analog 8-bromo-cAMP (8-BrcAMP) hypothalamically in satiated rats. Injection of 8-BrcAMP (10-100 nmol) into the perifornical (PFH) and lateral hypothalamus (LH) dose dependently stimulated food intake of up to 15.7 g in 2 h. Significantly smaller responses were obtained with thalamic injections. In contrast to the strong stimulatory effects of PFH and LH 8-BrcAMP, cAMP and 8-bromo-guanosine 3',5'-cyclic monophosphate (100 nmol) were ineffective, suggesting a chemically specific, intracellular action. Consistent with this, combined PFH injection of 7-deacetyl-7-O-(N-methylpiperazino)-tau-butyryl-forskolin dihydrochloride and 3-isobutyl-1-methylxanthine, agents that increase endogeneous cAMP, stimulated eating of up to 9.9 g in 2 h. These results demonstrate that increases in PFH/LH cAMP can elicit complex, goal-oriented behavior, suggesting an important role for cAMP in hypothalamic mechanisms stimulating food intake.
authors.affiliation: Department of Neuroscience, University of California at Riverside 92521, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Gillard
authors.forename: A M
authors.initials: AM
authors.lastname: Khan
authors.lastname: Ahsan-ul-Haq
authors.forename: R S
authors.initials: RS
authors.lastname: Grewal
authors.forename: B
authors.initials: B
authors.lastname: Mouradi
authors.forename: B G
authors.initials: BG
authors.lastname: Stanley
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004224:Diterpenes; D004435:Eating / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology*; D013238:Stereotaxic Techniques; D013788:Thalamus / Q000187:drug effects / Q000502:physiology
chemical_list: D004224:Diterpenes; C055627:L 858051; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine