Intracerebroventricular administration of 5,7-dihydroxytryptamine to mice increases both head-twitch response and the number of cortical 5-HT2 receptors.
5-Hydroxytryptamine-containing (5-HT) neurones in brain of the mouse were selectively destroyed by intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 micrograms). Sham-lesioned controls received vehicle (2 microliters, i.c.v.). Two weeks later the head-twitch response induced by 5-methoxy-N,N-dimethyltryptamine (2.0 mg/kg) and mediated by 5-HT2 receptors was markedly enhanced in the lesioned mice. Furthermore, lesioning also increased 5-HT2 binding sites in the cortex, assessed by the binding of [3H]ketanserin in these animals, and decreased levels of 5-HT in the cortex (70%) and mid/hindbrain (64%) regions. A second group of mice, lesioned with less 5,7-DHT (5-20 micrograms, i.c.v.) showed unaltered head-twitch responses to 5-methoxy-N, N-dimethyltryptamine (2.0 mg/kg) and did not have increased 5-HT2 receptor binding in the cortex. Depletions of 5-HT were 32 and 40% in the cortex and mid/hindbrain, respectively. Comparison of the extent of depletion of 5-HT in the mid/hindbrain after lesioning, with the increase in head-twitch response, suggested that depletions of less than 40% did not affect this behaviour. However, depletions greater than 40% produced marked increases in this response and there was a good correlation between these two variables (r=0.701, P less than 0.01). In conclusion, these data suggest that enhanced head-twitch responses occurring after lesioning with 5,7-DHT may result from increased 5-HT2 receptors in brain. Moreover, the magnitude of the observed behavioural enhancement was dependent upon the extent of depletion of 5-HT produced by the lesioning.
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004563:Electrochemistry; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011985:Receptors, Serotonin / Q000187:drug effects*
D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine