Complex Action of Antidepressant Treatment on Central Adrenergic System: Possible Relevance to Clinical Effects

Vetulani, Jerzy

doi:10.1055/s-2007-1017401

Cited by 37 publications

(15 citation statements)

References 9 publications

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“…Later, similar regulations were found in the central nervous system (CNS) (Ungerstedt 1971). antidepressant drugs (Vetulani 1984;Kostowski et al 1986). antidepressant drugs (Vetulani 1984;Kostowski et al 1986).…”

mentioning

confidence: 69%

Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

Minor¹,

Danysz

Jonsson³

et al. 1989

Pharmacology & Toxicology

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The acute effects of the alpha-2 adrenoceptor agonists, clonidine and guanfacine, upon antinociception, hypothermia and motor activity were compared under conditions of receptor antagonism, denervation, and chronic administration of a tricyclic antidepressant compound. The analgesic actions of clonidine and guanfacine were antagonised by idazoxan, an alpha-2 receptor antagonist, but potentiated by pretreatment with the noradrenaline neurotoxin DSP4, and attenuated by chronic treatment with desipramine (DMI). Clonidine- and guanfacine-induced hypothermia was antagonised by idazoxan, potentiated by prior treatment with DSP4 and attenuated by chronic administration with DMI. Both clonidine and guanfacine produced decreases in motor activity that were attenuated by idazoxan but unaffected by prior DSP-4 treatment. Chronic DMI administration also attenuated clonidine-induced hypoactivity but potentiated guanfacine-induced hypoactivity. These diverse results describe both similar and differential adaptive mechanisms modulating the functional effect of alpha-2 receptor systems in the central nervous system.

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mentioning

confidence: 69%

Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

Minor¹,

Danysz

Jonsson³

et al. 1989

Pharmacology & Toxicology

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“…Nevertheless, preclinical studies have noted several intriguing findings. For instance, chronic treatment with conventional antidepressants reduced the number of cortical β-adrenoreceptors (Koshikawa et al, 1989; Vetulani, 1984). In addition, the NMDA antagonists MK-801 (a non-competitive antagonist) and 1-aminocyclopropanecarboxylic acid (ACPC; a partial agonist at the glycine or co-activator site) both reduced [ 3 H] dihydroalprenolol binding to β-cortical adrenoreceptors (Klimek and Papp, 1994; Paul et al, 1992).…”

Section: Ampa and Nmda Receptors: Specific Findings In Mood Disordmentioning

confidence: 99%

New targets for rapid antidepressant action

Machado‐Vieira

Henter

Zarate

2017

Progress in Neurobiology

127

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Current therapeutic options for major depressive disorder (MDD) and bipolar disorder (BD) are associated with a lag of onset that can prolong distress and impairment for patients, and their antidepressant efficacy is often limited. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, and in the development of novel therapeutics for this disorder. The rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000. Since then, other NMDA receptor antagonists have been studied in MDD. Most have demonstrated relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics. This article reviews the clinical evidence supporting the use of novel glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (GluN2B)-specific NMDA receptor antagonists (CP-101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (GLYX-13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). We also briefly discuss several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy that have yet to be studied clinically; these include α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA) agonists and mGluR2/3 negative allosteric modulators. The review also discusses other promising, non-glutamatergic targets for potential rapid antidepressant effects, including the cholinergic system (scopolamine), the opioid system (ALKS-5461), corticotropin releasing factor (CRF) receptor antagonists (CP-316,311), and others.

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“…This theory is based principally on animal studies showing that changes brought about by different antidepressant treatments lead to a specific facilitation of neurotransmission involving alpha-1 adrenoceptors (Przegalinski, 1987;Vetulani, 1984). The relevant clinical data to support this view are scarce.…”

Section: Catecholaminergic Systems and Mechanismsmentioning

confidence: 99%

Clinical data and animal studies on adaptive receptor changes occurring in depression and after antidepressive treatment: A hypothesis of antidepressive action

Płaźnik

Kostowski

1993

Human Psychopharmacology

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The clinical and animal studies on the effects of antidepressant treatments on receptor-related changes in the functioning of central neurotransmitter systems, are reviewed. The great variability in individual clinical responses make it impossible to formulate one coherent hypothesis about adaptive receptor changes occurring in human beings. Nevertheless, it is concluded that neuroadaptive responses found in the catecholaminergic systems (dopaminergic and adrenergic alpha-1 receptors) might be important as the underlying mechanism for therapeutic efficacy in depression of antidepressant drugs (AD) and electroconvulsive shock treatment (ECS). The animal studies conducted in our laboratory over the last decade provide evidence for the existence of limbic neurotransmitter modulatory mechanism of action of AD and ECS. It is suggested that at least in the limbic areas (i.e. in the hippocampus and nucleus accumbens, the main structures of the mesolimbic system), AD and ECS produce bidirectional effects. On the one hand they were found to reduce 'inhibitory' signals mediated through serotonergic, GABA-ergic and alpha-2 adrenergic receptors while on the other hand they enhanced 'excitatory' central processes mediated via the dopaminergic and adrenergic alpha-1 receptors. Confirmation of this hypothesis was obtained from behavioral experiments (locomotor and exploratory activity), consisting of microinjections of selective receptor agonists and antagonists into the hippocampus and nucleus accumbens, following the chronic administration of different AD'S and ECS. We propose, therefore, that the mechanism of action of antidepressant therapies should be considered from the anatomical and receptor viewpoint, the crucial element being the 'tuning' of the signals within the limbic areas. The consequence of this mechanism is an enhancement of these processes which can be defined as 'activatory', in terms of their mood elevating effects. The final effect of antidepressant therapy emerges as a result of transmitter interactions and disinhibitory processes. The 'limbic modulatory neurotransmitter mechanism' is thus suggested to be responsible for the effect of antidepressant treatment.

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Complex Action of Antidepressant Treatment on Central Adrenergic System: Possible Relevance to Clinical Effects

Cited by 37 publications

References 9 publications

Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

Adaptive Changes in α‐2 Adrenoceptor Mediated Responses: Analgesia, Hypothermia and Hypoactivity

New targets for rapid antidepressant action

Clinical data and animal studies on adaptive receptor changes occurring in depression and after antidepressive treatment: A hypothesis of antidepressive action

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