8-OH-DPAT-induced hyperphagia: its neural basis and possible therapeutic relevance.
The pharmacological and neurochemical bases of hyperphagia induced by the serotonin agonist 8-OH-DPAT were examined. In addition, the possible therapeutic potential of 8-OH-DPAT and related drugs in the treatment of anorexic pathology was assessed in an animal model of anorexia (as induced by acute immobilization stress). In normal rats 8-OH-DPAT elicited feeding after peripheral injection and after intracerebral application to the brainstem raphé nuclei. Feeding elicited by peripheral injection of the drug was attenuated by pretreatment with the serotonin synthesis inhibitor para-chlorophenylalanine. Following a hyperphagic dose of 8-OH-DPAT, brain serotonin metabolism was reduced, particularly in midbrain and pons-medulla. Our interpretation of these data is that 8-OH-DPAT elicits feeding via an agonist action on serotonin autoreceptors in the raphé nuclei. These receptors are probably of the 5-HT1A subtype as 8-OH-DPAT has a high affinity for this receptor and other putative 5-HT1A agonist (i.e. buspirone, TVX Q 7821) also elicit feeding. In contrast, putative 5-HT1B agonists (i.e. RU-24969 and quipazine) decrease feeding and cause anorexia. 8-OH-DPAT and other 5-HT1A agonists attenuated the anorexia and body weight loss caused by immobilization stress. Therefore, it seems possible that 5-HT1A agonists may be clinically useful in the treatment of anorexia.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D000855:Anorexia / Q000188:drug therapy; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D010134:Fenclonine / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D001679:Biogenic Amines; D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010134:Fenclonine