Food restriction and streptozotocin treatment decrease 5-HT1A and 5-HT2A receptor-mediated behavioral effects in rats.
Food restriction and hypoinsulinemia can affect the synthesis, turnover, and receptor function of serotonin (5-HT) in brain. This study explored the effects of food restriction and streptozotocin treatment on behavioral effects related to 5-HT1A (+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) and 5-HT2A [(+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)] receptor activation. Lower lip retraction and flat body posture (8-OH-DPAT) and head twitching (DOI) were measured in rats during free feeding, food restriction, after treatment with streptozotocin, and finally after insulin replacement. 8-OH-DPAT induced lower lip retraction and flat body posture whereas DOI induced head twitching. One week of food restriction (10 g/day) decreased 8-OH-DPAT-induced lower lip retraction, 8-OH-DPAT-induced flat body posture, and DOI-induced head twitching. Subsequently, 1 week of free access to food restored sensitivity to 8-OH-DPAT and DOI-induced behavioral effects. Finally, 1 week after streptozotocin, 8-OH-DPAT-induced flat body posture and DOI-induced head twitching were markedly reduced whereas 8-OH-DPAT-induced lower lip retraction was unchanged. One week of insulin replacement restored sensitivity to 8-OH-DPAT and DOI-induced behavioral effects. These results show that modest food restriction or experimentally induced diabetes can profoundly affect sensitivity to drugs acting at 5-HT1A or 5-HT2A receptors; these results could be relevant to understanding the comorbidity of depression and diabetes.
Li
Jun-Xu
JX
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
France
Charles P
CP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005508:Food Deprivation; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D013311:Streptozocin
D000662:Amphetamines; D007004:Hypoglycemic Agents; D007328:Insulin; D044402:Receptor, Serotonin, 5-HT2A; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D013311:Streptozocin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine