Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: Studies on the role of presynaptic α2-adrenoceptors

G. Sacchetti, M. Bernini, M. Gobbi, S. Parini, L. Pirona, T. Mennini, R. Samanin

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the α2-adrenoceptor agonist clonidine at the dose of 10 μg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 μg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 μM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to α2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of α2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.

Original languageEnglish
Pages (from-to)66-72
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume363
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Desipramine
Adrenergic Receptors
Hippocampus
Norepinephrine
Clonidine
Therapeutics
Locus Coeruleus
Injections
Adrenergic Neurons
Autoreceptors
Synaptosomes
Autoradiography
Antidepressive Agents
Control Groups

Keywords

  • α-Adrenoc eptor desensitization
  • [H]Noradrenaline uptake
  • Clonidine
  • Desipramine
  • Dorsal hippocampus
  • Locus coeruleus
  • Microdialysis
  • Noradrenaline

ASJC Scopus subject areas

  • Pharmacology

Cite this

Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus : Studies on the role of presynaptic α2-adrenoceptors. / Sacchetti, G.; Bernini, M.; Gobbi, M.; Parini, S.; Pirona, L.; Mennini, T.; Samanin, R.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 363, No. 1, 2001, p. 66-72.

Research output: Contribution to journalArticle

@article{a0ab05234aa048df968de733f535384e,
title = "Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: Studies on the role of presynaptic α2-adrenoceptors",
abstract = "Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the α2-adrenoceptor agonist clonidine at the dose of 10 μg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 μg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 μM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to α2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17{\%}) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of α2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.",
keywords = "α-Adrenoc eptor desensitization, [H]Noradrenaline uptake, Clonidine, Desipramine, Dorsal hippocampus, Locus coeruleus, Microdialysis, Noradrenaline",
author = "G. Sacchetti and M. Bernini and M. Gobbi and S. Parini and L. Pirona and T. Mennini and R. Samanin",
year = "2001",
doi = "10.1007/s002100000334",
language = "English",
volume = "363",
pages = "66--72",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus

T2 - Studies on the role of presynaptic α2-adrenoceptors

AU - Sacchetti, G.

AU - Bernini, M.

AU - Gobbi, M.

AU - Parini, S.

AU - Pirona, L.

AU - Mennini, T.

AU - Samanin, R.

PY - 2001

Y1 - 2001

N2 - Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the α2-adrenoceptor agonist clonidine at the dose of 10 μg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 μg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 μM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to α2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of α2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.

AB - Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the α2-adrenoceptor agonist clonidine at the dose of 10 μg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 μg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 μM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to α2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of α2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.

KW - α-Adrenoc eptor desensitization

KW - [H]Noradrenaline uptake

KW - Clonidine

KW - Desipramine

KW - Dorsal hippocampus

KW - Locus coeruleus

KW - Microdialysis

KW - Noradrenaline

UR - http://www.scopus.com/inward/record.url?scp=0035166942&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035166942&partnerID=8YFLogxK

U2 - 10.1007/s002100000334

DO - 10.1007/s002100000334

M3 - Article

C2 - 11191838

AN - SCOPUS:0035166942

VL - 363

SP - 66

EP - 72

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 1

ER -