Stimulation of 5-HT1A receptors in the dorsal hippocampus impairs acquisition and performance of a spatial task in a water maze.
8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a potent 5-HT1A receptor agonist, was infused in the dorsal hippocampus of rats and its effect on acquisition and performance of a 2-platform spatial discrimination task was studied using a water maze. The infusion (0.5 microliter/min) of 2 but not 0.4 microgram 8-OH-DPAT in the CA1 region of the dorsal hippocampus impaired rats' accuracy with no effect on latency (except day 3). At 5 micrograms 8-OH-DPAT impaired rats' accuracy and significantly increased choice latencies from day 2 to day 5 of the training period. The dose of 2 micrograms significantly increased the errors of omissions on the first day of training and animals which had received 5 micrograms 8-OH-DPAT made significantly more errors of omission on the first and second days of training. Intrahippocampal administration of 1 microgram spiroxatrine, a 5-HT1A receptor antagonist, antagonized the effect of 5 micrograms 8-OH-DPAT on accuracy and choice latency with no significant effect on the errors of omission on days 1 and 2 of training. Infusion of 2 and 5 micrograms 8-OH-DPAT in the dorsal hippocampus also impaired accuracy in well-trained rats. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus causes an impairment of spatial discrimination in rats.
Carli
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Lazarova
M
M
Tatarczynska
E
E
Samanin
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D004146:Dioxanes / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology; D013238:Stereotaxic Techniques
D004146:Dioxanes; D018492:Dopamine Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C018387:spiroxatrine