A pharmacological analysis of the eating response induced by 8-OH-DPAT injected into the dorsal raphé nucleus reveals the involvement of a dopaminergic mechanism.
Direct injection of the 5-hydroxytryptamine (5-HT) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the dorsal raphé nucleus (DRN) dose dependently increased food intake in free feeding rats. The hypothesis that this effect is mediated by 5-HT1A receptors was tested by investigating the abilities of the putative 5-HT1A antagonists metergoline, propranolol and spiperone to prevent 8-OH-DPAT-induced eating. Metergoline failed to affect 8-OH-DPAT-induced eating when injected either peripherally or into the DRN. Peripherally injected propranolol and spiperone prevented 8-OH-DPAT-induced eating, but these drugs were ineffective when injected into the DRN. These results indicate that 8-OH-DPAT-induced eating may not involve 5-HT1A receptors within the DRN. The ability of peripherally injected spiperone to prevent the eating response to 8-OH-DPAT reflects its dopamine blocking activity since haloperidol was an effective antagonist of 8-OH-DPAT-eating. This result may indicate that 8-OH-DPAT produces a general behavioural activation by reducing the inhibitory influence which 5-HT normally exerts over the nigrostriatal dopamine pathway, and that this behavioural activation is expressed as eating when food is the most salient goal object present.
Fletcher
P J
PJ
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Davies
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D008711:Metergoline; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol; D006220:Haloperidol; D004298:Dopamine