The behavioral effects of depletions of brain serotonin induced by 5,7-dihydroxytryptamine vary with time after administration.
Ether-anesthetized Sprague-Dawley rats were depleted of brain serotonin (5HT) by intraventricular injections of 50 micrograms 5,7-dihydroxtryptamine (57DHT). Oral pretreatment with 25 mg/kg desmethylimipramine was used to protect brain noradrenergic neurons from 57DHT. Liquid chromatographic assays revealed that this treatment did not significantly alter catecholamine levels but depleted hippocampal 5HT by 92% and striatal 5HT by 45%. Three or eleven days after lesioning, locomotor and exploratory behavior was characterized in separate groups of animals with a behavioral pattern monitor (BPM). On Days 4 and 12, the animals were retested following saline or 1.0 mg/kg amphetamine. Three days after depletion, lesioned rats exhibited a decrease rate of habituation of locomotor activity relative to controls. When challenged with amphetamine (1.0 mg/kg), 5HT-depleted rats exhibited increased corner and decreased center activity, as well as stereotyped patterns of locomotion. Eleven days following lesion, 5HT-depleted rats exhibited habituation rates greater than controls; amphetamine challenge yielded patterns of activity similar to those of control animals. These results show that central serotonergic pathways play an important role in modulating both spontaneous and amphetamine-elicited activity in rats, and that compensatory mechanisms operate over time to alter the behavioral effects of 57DHT-induced depletions of brain 5HT.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D006624:Hippocampus / Q000032:analysis; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000502:physiology*
D004102:Dihydroxytryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000661:Amphetamine; D003891:Desipramine; D009638:Norepinephrine