The potentiation of amphetamine-induced hyperlocomotion by fimbria-fornix lesions in rats is abolished by intrahippocampal grafts rich in serotonergic neurons.
Three-month old Long-Evans female rats were submitted to aspirative lesions of the fimbria-fornix and intrahippocampal grafts of a cell suspension prepared from a region of the fetal brain including the septum and the diagonal band of Broca (rich in cholinergic neurons) or the raphe (rich in serotonergic neurons). A group of lesioned rats was grafted with both suspensions mixed. Lesion-only and sham-operated rats served as controls. Four months after the lesions, all rats were tested daily for locomotor activity in their home cage, 1 day without being injected, 2 days with an injection of NaCl and 5 days with an injection of 1 mg/kg (i.p.) d-amphetamine. The effects of the lesions and grafts were assessed by measuring the accumulation of [3H]-choline or [3H]-5-hydroxytryptamine (5-HT) by hippocampal slices, and the electrically-evoked release of tritium. Amphetamine injections produced hyperlocomotion which was potentiated by the lesion. This lesion-induced potentiation was also found in rats with septal grafts, but not in those with raphe or co-grafts. The uptake and electrically-evoked release of [3H]-acetylcholine or [3H]-5-HT were reduced in hippocampal slices from lesion-only rats. In rats which received grafts of septal cells or co-grafts, but not in those with raphe grafts, uptake and release of [3H]-acetylcholine were close to normal. Uptake and release of [3H]-5-HT were close to normal in rats with raphe grafts or with co-grafts, but not in those with septal grafts. Altogether, these data suggest that damage to the serotonergic afferents of the hippocampus might play some role in the potentiation of amphetamine-induced hyperlocomotion associated with fimbria-fornix lesions.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001927:Brain Diseases / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002794:Choline / Q000378:metabolism; D004357:Drug Synergism; D004558:Electric Stimulation; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000196:embryology; D006624:Hippocampus / Q000378:metabolism / Q000601:surgery*; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation*; D051381:Rats; D020318:Rats, Long-Evans; D012688:Septum Pellucidum / Q000166:cytology / Q000196:embryology; D012701:Serotonin / Q000378:metabolism*