Abstract
The antagonism of hypothermia induced by two doses of apomorphine (1 to 16 mg/kg) is proposed as an improved screening test for both neuroleptics and antidepressants. Low dose apomorphine-induced hypothermia (1 mg/kg) differentiates sulpiride-like neuroleptics (which better antagonize this effect of apomorphine than other effects such as stereotyped behavior) from haloperidol-like drugs. The latter equally antagonize the two effects of apomorphine. The effects of sulpiride are also distinct from those of chlorpromazine-like drugs which strongly antagonize stereotyped behavior, but not hypothermia induced by apomorphine. Hypothermia induced by a high dose of apomorphine (16 mg/kg) is not antagonized by neuroleptics, but is strongly antagonized by antidepressants (imipramine-like drugs, amineptine, amoxapine, nomifensine, viloxazine) and potential antidepressants (beta-adrenergic stimulants). The use of these two tests rapidly screens both antidepressants and neuroleptics and classifies neuroleptics according to their profile of action on the dopaminergic system.
MeSH Terms
Animals
Antidepressive Agents/pharmacology
Antipsychotic Agents/pharmacology
Apomorphine/antagonists & inhibitors,pharmacology
Drug Evaluation, Preclinical/methods
Humans
Hypothermia/chemically induced
Male
Mice
Mice, Inbred Strains
Receptors, Adrenergic/drug effects
Receptors, Dopamine/drug effects
Stereotyped Behavior/drug effects
Chemicals
Antidepressive Agents
Antipsychotic Agents
Receptors, Adrenergic
Receptors, Dopamine
Apomorphine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Puech A J
Chermat R
Poncelet M
Doaré L
Simon P
References (15)
15 references, click to expand
-
Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum.
J Pharm Pharmacol. 1974 May;26(5):370-1
PMID: 4152974
-
A beta adrenergic stimulant (salbutamol) versus clomipramine in depression: a controlled study.
Br J Psychiatry. 1980 Apr;136:354-8
PMID: 6992902
-
The effect of tricyclic antidepressants on apomorphine-induced hypothermia in the mouse.
Pol J Pharmacol Pharm. 1974 May-Jun;26(3):329-36
PMID: 4854785
-
Amoxapine in experimental psychopharmacology: a neuroleptic or an antidepressant?
Arzneimittelforschung. 1979;29(5):814-20
PMID: 40575
-
IS IT POSSIBLE TO PREDICT THE CLINICAL EFFECTS OF NEUROLEPTIC DRUGS (MAJOR TRANQUILLIZERS) FROM ANIMAL DATA?I. "NEUROLEPTIC ACTIVITY SPECTRA" FOR RATS.
Arzneimittelforschung. 1965 Feb;15:104-17
PMID: 14268414
-
Imipramine antagonism of apomorphine-induced hypothermia: a non-dopaminergic interaction.
Eur J Pharmacol. 1978 Jan 1;47(1):125-7
PMID: 618727
-
Proceedings: Neurotropic effects of thyrotropin releasing hormone (TRH).
Naunyn Schmiedebergs Arch Pharmacol. 1974;282(Suppl):suppl 282:R51
PMID: 4276591
-
Serotonergic component of neuroleptic receptors.
Nature. 1978 Mar 9;272(5649):168-71
PMID: 564466
-
Possible involvement of brain serotonin in apomorphine-induced hypothermia.
Eur J Pharmacol. 1973 Jul;23(1):82-9
PMID: 4270157
-
Benzamides and classical neuroleptics: comparison of their actions using 6 apomorphine-induced effects.
Eur J Pharmacol. 1978 Aug 15;50(4):291-300
PMID: 29758
-
Antagonism by d,1-propranolol of imipramine effects in mice.
Eur J Pharmacol. 1979 Nov 23;60(1):105-8
PMID: 520412
-
Evidence for dopamine receptors mediating sedation in the mouse brain.
Nature. 1976 Dec 9;264(5586):564-7
PMID: 1004597
-
Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release.
Br J Pharmacol. 1977 Aug;60(4):481-97
PMID: 20190
-
L-DOPA, catecholamines, and behavior: a clinical and biochemical study in depressed patients.
Biol Psychiatry. 1970 Oct;2(4):341-66
PMID: 4920729
-
The effect of some new antidepressants on apomorphine-induced hypothermia in mice.
J Pharm Pharmacol. 1979 Aug;31(8):560-1
PMID: 40002