The effects of centrally acting adrenergic agonists on temperature and on explorative and motor behaviour. Relation with effects on quasi-morphine withdrawal behaviour

Laan, Jan Willem van der; Veenendaal, Willem Van; Voorthuis, Paul; Weick, Gradus; Hillen, F. C.

doi:10.1016/0014-2999(85)90264-x

Cited by 17 publications

(12 citation statements)

References 14 publications

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“…The present data support the a2-adrenoceptors involvement in the hypothermic action of both clonidine and guanfacine, since it was antagonized by a low dose of yohimbine and idazoxan. The a2-adrenoceptors involved in the hypothermic action of clonidine were found previously (Zacny 1982), but note also that the hypothermic action is shared by all a2-agonists tested so far (Van der Laan et al 1985;Virtanen & MacDonald 1985). It has been suggested that central postsynaptic a2-adrenoceptors, probably located in the hypothalamus, are mainly involved in the hypothermic action of clonidine (McLennan 1981;Lin et al 1984;Danysz et al 1985).…”

Section: -supporting

confidence: 64%

Chronic Treatment with Antidepressant Drugs and ECT Differentially Modifies the Hypothermic Action of Clonidine and Guanfacine

Danysz

Minor

Mohammed

et al. 1987

Pharmacology & Toxicology

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The hypothermia inducing action of clonidine and guanfacine was abolished by yohimbine and idazoxan pretreatment which suggests an alpha 2-adrenoceptor involvement in this effect. The effects of acute and chronic treatment with the antidepressant drugs desipramine (DMI), amitriptyline (AMI), maprotiline (MAP), mianserin (MIAN), iprindol (IPR), alaproclate (ALA) and electroconvulsive treatment (ECT) on the hypothermic action of the alpha 2-adrenoceptor agonists clonidine and guanfacine were studied. Acute administration of MIAN potentiated clonidine induced hypothermia whereas acute MIAN, IPR and ALA potentiated guanfacine induced hypothermia. Repetitive DMI, AMI and MAP treatment attenuated clonidine-induced hypothermia whereas guanfacine-induced hypothermia was potentiated by chronic treatment with DMI, AMI, MAP and MIAN, ECT applied without anaesthesia attenuated both clonidine and guanfacine hypothermia, however, under ethyl ether anaesthesia ECT was effective only towards guanfacine hypothermia. This discrepancy is discussed in terms of the relative selectivity of the agonists used, the reliability of agonist studies for indexing receptor function, and possible pharmacokinetic interaction.

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Section: -supporting

confidence: 64%

Chronic Treatment with Antidepressant Drugs and ECT Differentially Modifies the Hypothermic Action of Clonidine and Guanfacine

Danysz

Minor

Mohammed

et al. 1987

Pharmacology & Toxicology

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“…In the present study, the rotarod test, which has been previously used as a measure of both sedation and motor impairment 24 , was used to assess the sedative and/or motoric effects of the agonists or their combination immediately after SP nociceptive testing. In outbred ICR mice (fig.…”

Section: Resultsmentioning

confidence: 99%

Clonidine and Dexmedetomidine Produce Antinociceptive Synergy in Mouse Spinal Cord

Fairbanks

Kitto²,

Nguyen³

et al. 2009

Anesthesiology

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Background Synergy between drugs manifests with increased potency and/or efficacy of the combination relative to either agonist given alone. Synergy is typically observed between drugs of different classes, as is the case with the alpha-adrenergic-opioid receptor synergy often observed in preclinical studies. However, rare studies report synergy between agonists of the same class. The present study examined the analgesic interaction between two intrathecally injected alpha-2 adrenergic receptor (AR) agonists previously thought to act at the same receptor subtype when given spinally. Methods Mice were administered clonidine, dexmedetomidine, or the combination spinally to evaluate the interaction between these two agonists. The ED50 values were calculated and the interactions tested by isobolographic analysis. The rotarod test was performed in the same mice following the completion of analgesic assessment to assess motor or sedative effects. These experiments were performed in outbred mice as well as in mice with mutant alpha2A-ARs, alpha2C-AR-knock-out or wildtype controls. Finally, analgesic cross-tolerance between clonidine and dexmedetomidine was evaluated. Results Clonidine and dexmedetomidine interacted synergistically in all lines except the alpha2C-AR knockout line, implicating alpha2C-ARs in the interaction. Additionally, clonidine and dexmedetomidine did not show analgesic cross-tolerance in the outbred strain, suggesting that the two drugs have distinct mechanisms of action. Conclusions The present study introduces a new synergistic agonist pair, clonidine – dexmedetomidine. These two drugs appear to require the alpha2A-AR for spinal analgesia when given separately; when delivered as a combination, the resultant synergistic interaction requires the alpha2C-AR as well.

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“…The vehicle control for the DOPS experiment was also administered 5 h before testing (Rommelfanger et al 2007;Schank et al 2008;Thomas et al 1998). The doses for all compounds tested were based on previous studies (Durcan et al 1989;Ji et al 2014;Kauppila et al 1991;Luttinger et al 1985;Millan et al 2000;Murchison et al 2004;Rudoy et al 2007;Schank et al 2008;Schroeder et al 2013;Stemmelin et al 2008;Van Der Laan et al 1985) and optimized in pilot experiments to ensure that behavioral effects were not due to sedation.…”

Section: Drugsmentioning

confidence: 99%

Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder

Lustberg

Iannitelli

Tillage

et al. 2019

Preprint

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AbstractRationaleObsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated by stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior cingulate cortex (ACC) can provide symptomatic relief. Although the ACC receives noradrenergic innervation and expresses adrenergic receptors (ARs), the involvement of norepinephrine (NE) in OCD has not been investigated.ObjectiveTo determine the effects of genetic or pharmacological disruption of NE neurotransmission on marble burying (MB) and nestlet shredding (NS) in two animal models of OCD.MethodsWe assessed NE-deficient (Dbh -/-) mice and NE-competent (Dbh +/-) controls in MB and NS tasks. We also measured the effects of anti-adrenergic drugs on NS and MB in control mice and the effects of pharmacological restoration of central NE in Dbh -/- mice. Finally, we compared c-fos induction in the locus coeruleus (LC) and ACC of Dbh -/- and control mice following both tasks.ResultsDbh -/- mice virtually lacked MB and NS behaviors seen in control mice but did not differ in the elevated zero maze (EZM) model of general anxiety-like behavior. Pharmacological restoration of central NE synthesis in Dbh -/- mice completely rescued NS behavior, while NS and MB were suppressed in control mice by anti-adrenergic drugs. Expression of c-fos in the ACC was attenuated in Dbh -/- mice after MB and NS.ConclusionThese findings support a role for NE transmission to the ACC in the expression of stress-induced compulsive behaviors and suggest further evaluation of anti-adrenergic drugs for OCD is warranted.

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The effects of centrally acting adrenergic agonists on temperature and on explorative and motor behaviour. Relation with effects on quasi-morphine withdrawal behaviour

Cited by 17 publications

References 14 publications

Chronic Treatment with Antidepressant Drugs and ECT Differentially Modifies the Hypothermic Action of Clonidine and Guanfacine

Chronic Treatment with Antidepressant Drugs and ECT Differentially Modifies the Hypothermic Action of Clonidine and Guanfacine

Clonidine and Dexmedetomidine Produce Antinociceptive Synergy in Mouse Spinal Cord

Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder

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