Monoaminergic denervation of the rat hippocampus: Microiontophoretic studies on pre- and postsynaptic supersensitivity to norepinephrine and serotonin |
| |
Authors: | C. De Montigny R.Y. Wang T.A. Reader G.K. Aghajanian |
| |
Affiliation: | aCentre de Recherche en Sciences Neurologiques, Département de Physiologie, Universitéde Montréal Montréal H3C 3J7 Québec, Canada b(R.Y.W.) Department of Pharmacology, St. Louis University School of Medicine, St. Louis. Mo., 63104, USA c(G.K.A.) Departments of Psychiatry and Pharmacology, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Conn. 06508, U.S.A. |
| |
Abstract: | The responsiveness of hippocampal CA3 pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE), γ-aminobutyric acid (GABA) and isoproterenol (ISO) was assessed in rats following 5,7-dihydroxy-tryptamine (5,7-DHT) and 6-hydroxydopamine (6-OHDA) pretreatments and bilateral locus coeruleus lesions. The intraventricular administration of 200 μg (free base) of 5,7-DHT and of 6-OHDA produced 89% and 93% decreases of 5-HT and NE respectively. None of these pretreatments modified the initial responsiveness to, or recovery from iontophoretic application of 5-HT. In 6-OHDA pretreated and locus-lesioned rats, the initial effectiveness of NE was not altered but its effect was markedly prolonged. However, there was no such prolongation of the effect of ISO which is not a substrate for the high affinity NE reuptake. The effect of GABA was not affected by these pretreatments. Acute pharmacological blockade of the NE reuptake with desipramine (5 mg/kg, i.p.) similarly induced a prolongation of the effect of iontophoretically applied NE, while fluoxetine (10 mg/kg, i.p.) a 5-HT reuptake blocker, failed to alter the recovery of pyramidal cells from iontophoretic application of 5-HT. It is concluded that 5-HT denervation induces neither pre- nor postsynaptic types of supersensitivity in hippocampal pyramidal cells, contrasting with the previously shown supersensitivity of ventral lateral geniculate and amygdaloid neurons following 5-HT denervation. NE denervation fails to induce a postsynaptic type of supersensitivity but leads to a marked prolongation of the response to NE indicative of a presynaptic mechanism. These results underscore the necessity for regional studies of neurotransmitters and drug action. |
| |
Keywords: | amygdala luteinizing hormone electrical stimulation microinjection testosterone estradiol 5α-dihydrotestosterone catecholestrogen male pig |
本文献已被 ScienceDirect 等数据库收录! |
|