On the supersensitivity of dopamine receptors, induced by neuroleptics
Abstract
Different neuroleptics caused dopamine receptor blockade (antagonism against methylphenidate-induced compulsive gnawing) for varying lengths of time. When the receptor blockade had expired, supersensitivity to dopamine agonists (occurrence of apomorphine-induced compulsive gnawing and enhancement of methylphenidate-induced gnawing) developed and persisted for varying periods of time. The degree and duration of supersensitivity was related to the degree and duration of the preceding receptor blockade. Inhibition of catecholamine or 5-HT synthesis had no influence on development of supersensitivity. Stimulation with a dopamine agonist, apomorphine, during the period of the development of supersensitivity did not modify the enhanced receptor supersensitivity. A cholinergic-dopaminergic balance was shown to be involved in the manifestation of compulsive behavior during the supersensitivity phase. Tolerance to the dopamine antagonistic effect of a neuroleptic also developed after a single neuroleptic treatment, most likely due to increased sensitivity of the receptors for the dopamine agonist. It is concluded, that the dopamine receptor blockade induced by a single dose of a neuroleptic agent is a dynamic phenomenon which in the course of time is replaced by an increased sensitivity of the receptors to dopamine agonists. Noradrenergic or 5-HT neuron systems do not seem to be involved in the neuroleptic-induced supersensitivity, whereas a dopaminergic-cholinergic balance is operative in the supersensitivity situation.
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The use of ketamine in psychiatry is at risk of replicating the 2016 opioid US epidemic abuse with the risk to induce neurotoxicity, which might be associated with persistent post-withdrawal disorders.
“In view of the inevitable decay of the response to ketamine due to pharmacological tolerance [148] and its possible benefit as maintenance therapy in treatment-resistant depression [142], and considering that some clinicians use ketamine formulations for chronic use despite the alarm regarding 'the rapid proliferation of off-label ketamine administration in the absence of evidence of”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [148]
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References 28 · Cited by 134
- Authors
- Christensen, A. V., Fjalland, B., & Nielsen, I. M.
- Affiliations
- Lundbeck (Denmark) (DK)
- Venue
- Psychopharmacology
- Published
- 1976
- Volume
- 48
- Issue
- 1
- Pages
- 1-6
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2025081012
- Cited by
- 134
- References
- 28
- Citations by year
- 2024: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- dopamine receptor supersensitivity, antipsychotic drugs, dopamine receptor blockade, dopamine agonists, apomorphine, methylphenidate, compulsive behavior, catecholamine synthesis inhibition, serotonin synthesis inhibition
- MeSH terms
- Animals, Apomorphine, Dopamine, Drug Tolerance, Humans, Male, Methylphenidate, Receptors, Drug, Stereotyped Behavior, Tranquilizing Agents, Neurotransmitter Agents, Mice
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