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Facilitation of amphetamine‐induced hypothermia in mice by GABA agonists and CCK‐8
Author(s) -
Boschi Gabrielle,
Launay Nicole,
Rips Richard
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12288.x
Subject(s) - chemistry , pharmacology , agonist , quipazine , hypothermia , amphetamine , endocrinology , picrotoxin , dopamine , medicine , bicuculline , serotonin , 5 ht receptor , receptor , gabaa receptor , biochemistry
1 Amphetamine‐induced hypothermia in mice is facilitated by dopaminergic stimulation and 5‐hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the γ‐aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK‐8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine‐induced hypothermia to certain neuroleptics. 2 Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine‐induced hypothermia. The GABA B agonist, baclofen (2.5 mg kg −1 , i.p.) potentiated this hypothermia, whereas the GABA A agonist, muscimol, did not. γ‐Butyrolactone (GBL) (40 mg kg −1 , i.p.) and the neuropeptide CCK‐8 (0.04 mg kg −1 , i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3 Dopamine itself (3, 9, 16 and 27 μg, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine‐induced hypothermia, but pimozide (4 mg kg −1 , i.p.), cis (z)flupentixol (0.25 mg kg −1 , i.p.) and haloperidol (5 μg, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5‐hydroxytryptamine (5‐HT) receptor blocker, cyproheptadine, nor the inhibitor of 5‐HT synthesis, p ‐chlorophenylalanine (PCPA), modified dopamine‐induced hypothermia. Fluoxetine, an inhibitor of 5‐HT. reuptake, had no effect, whereas quipazine (6 mg kg −1 , i.p.), a 5‐HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK‐8. 4 These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5‐hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK‐8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamine‐induced hypothermia to some neuroleptics, while dopamine‐induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences.