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Functional activity of intrahippocampal septal grafts is regulated by catecholaminergic host afferents as studied by microdialysis of acetylcholine

Leanza, G LU ; Nilsson, O G LU and Björklund, A LU (1993) In Brain Research 618(1). p.47-56
Abstract

Previous microdialysis experiments have shown that acetylcholine (ACh) release from septal grafts in the hippocampus of awake rats is influenced by the behaviour of the animals, which strongly suggests that the host brain can exert a regulatory control over the activity of the grafted neurons. Since the activity of the normal septo-hippocampal cholinergic system is likely to be regulated, in part, by brainstem catecholaminergic afferents, we wished to study the effect of catecholaminergic drugs on ACh release in the hippocampus reinnervated by septal grafts. Rats were subjected to a unilateral aspirative fimbria-fornix (FF) transection and grafted with tissue from the fetal septal-diagonal band area, either as a cell suspension... (More)

Previous microdialysis experiments have shown that acetylcholine (ACh) release from septal grafts in the hippocampus of awake rats is influenced by the behaviour of the animals, which strongly suggests that the host brain can exert a regulatory control over the activity of the grafted neurons. Since the activity of the normal septo-hippocampal cholinergic system is likely to be regulated, in part, by brainstem catecholaminergic afferents, we wished to study the effect of catecholaminergic drugs on ACh release in the hippocampus reinnervated by septal grafts. Rats were subjected to a unilateral aspirative fimbria-fornix (FF) transection and grafted with tissue from the fetal septal-diagonal band area, either as a cell suspension injection into the depth of the hippocampus or as a solid implant in the FF lesion cavity. Microdialysis of ACh release was carried out 17-20 months after transplantation in awake, freely-moving animals. The reduction in steady-state ACh overflow induced by the FF lesion (-81%) was restored to normal or above normal levels in rats with either solid or suspension grafts. In normal rats, systemic administration of apomorphine (2.0 mg/kg, s.c.) or amphetamine (2.5 mg/kg, i.p.) caused a 3.7 (+189%) or 7.8 (+301%) pmol/15 min increase in ACh overflow compared to the previous baseline level, respectively. The drug-induced increases in ACh levels in the FF-lesioned controls was substantially lower than normal (86-89% reduction). Both apomorphine and amphetamine resulted in an approximately two-fold increase in hippocampal ACh release in rats with suspension grafts. These responses were significantly increased over those seen in rats with FF lesions only, but they tended to be lower and more variable than normal. Rats with solid septal grafts responded significantly stronger than FF lesion controls to amphetamine with two-fold increased ACh overflow, whereas the response to apomorphine was less clear-cut. Pretreatment with the catecholamine synthesis blocker alpha-methyl-p-tyrosine (AMPT; 200 mg/kg x 3) did not affect steady-state or apomorphine-stimulated release of ACh in any of the groups, whereas the effect of amphetamine was abolished in both normal and grafted rats. The results suggest that ACh release derived from septal grafts in the hippocampus, similar to the normal septo-hippocampal system, can be affected by manipulations of the host catecholaminergic systems. This mechanism may, at least in part, underlie the ability of the host brain to influence and control the activity of grafted cholinergic neurons.

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Acetylcholine/administration & dosage, Afferent Pathways/drug effects, Amphetamine/pharmacology, Animals, Apomorphine/pharmacology, Catecholamines/metabolism, Female, Fetal Tissue Transplantation, Hippocampus, Methyltyrosines/pharmacology, Microdialysis, Rats, Rats, Sprague-Dawley, Receptors, Dopamine/drug effects, Septum Pellucidum/transplantation, Transplantation, Heterotopic, Tyrosine 3-Monooxygenase/antagonists & inhibitors, alpha-Methyltyrosine
in
Brain Research
volume
618
issue
1
pages
47 - 56
publisher
Elsevier
external identifiers
  • pmid:8104663
ISSN
0006-8993
DOI
10.1016/0006-8993(93)90427-o
language
English
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yes
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ea83713e-eaf9-4cef-b156-8dccaa415c65
date added to LUP
2019-06-25 09:59:09
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2019-12-25 04:02:58
@article{ea83713e-eaf9-4cef-b156-8dccaa415c65,
  abstract     = {<p>Previous microdialysis experiments have shown that acetylcholine (ACh) release from septal grafts in the hippocampus of awake rats is influenced by the behaviour of the animals, which strongly suggests that the host brain can exert a regulatory control over the activity of the grafted neurons. Since the activity of the normal septo-hippocampal cholinergic system is likely to be regulated, in part, by brainstem catecholaminergic afferents, we wished to study the effect of catecholaminergic drugs on ACh release in the hippocampus reinnervated by septal grafts. Rats were subjected to a unilateral aspirative fimbria-fornix (FF) transection and grafted with tissue from the fetal septal-diagonal band area, either as a cell suspension injection into the depth of the hippocampus or as a solid implant in the FF lesion cavity. Microdialysis of ACh release was carried out 17-20 months after transplantation in awake, freely-moving animals. The reduction in steady-state ACh overflow induced by the FF lesion (-81%) was restored to normal or above normal levels in rats with either solid or suspension grafts. In normal rats, systemic administration of apomorphine (2.0 mg/kg, s.c.) or amphetamine (2.5 mg/kg, i.p.) caused a 3.7 (+189%) or 7.8 (+301%) pmol/15 min increase in ACh overflow compared to the previous baseline level, respectively. The drug-induced increases in ACh levels in the FF-lesioned controls was substantially lower than normal (86-89% reduction). Both apomorphine and amphetamine resulted in an approximately two-fold increase in hippocampal ACh release in rats with suspension grafts. These responses were significantly increased over those seen in rats with FF lesions only, but they tended to be lower and more variable than normal. Rats with solid septal grafts responded significantly stronger than FF lesion controls to amphetamine with two-fold increased ACh overflow, whereas the response to apomorphine was less clear-cut. Pretreatment with the catecholamine synthesis blocker alpha-methyl-p-tyrosine (AMPT; 200 mg/kg x 3) did not affect steady-state or apomorphine-stimulated release of ACh in any of the groups, whereas the effect of amphetamine was abolished in both normal and grafted rats. The results suggest that ACh release derived from septal grafts in the hippocampus, similar to the normal septo-hippocampal system, can be affected by manipulations of the host catecholaminergic systems. This mechanism may, at least in part, underlie the ability of the host brain to influence and control the activity of grafted cholinergic neurons.</p>},
  author       = {Leanza, G and Nilsson, O G and Björklund, A},
  issn         = {0006-8993},
  language     = {eng},
  month        = {07},
  number       = {1},
  pages        = {47--56},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Functional activity of intrahippocampal septal grafts is regulated by catecholaminergic host afferents as studied by microdialysis of acetylcholine},
  url          = {http://dx.doi.org/10.1016/0006-8993(93)90427-o},
  doi          = {10.1016/0006-8993(93)90427-o},
  volume       = {618},
  year         = {1993},
}