1. The hydroxylated metabolites of
amphetamine,
p-hydroxyamphetamine (p-OHA) and
p-hydroxynorephedrine (p-OHN), were administered intracerebroventricularly in mice in order to evaluate their ability to elicit
hypothermia. 2. Intracerebroventricular (i.c.v.) administration of p-OHA and p-OHN (1, 3 and 9 micrograms/mouse) induced maximal
hypothermia 30 min after injection. p-OHA and p-OHN (9 micrograms, i.c.v.) produced maximal decreases in rectal temperature of -6.48 +/- 0.44 degrees C and -3.82 +/- 0.42 degrees C, respectively. Both metabolites are more effective than
amphetamine (at 9 micrograms, i.c.v., -3.32 +/- 0.75 degrees C). 3. Pretreatment with
haloperidol (5 micrograms, i.c.v.) suppressed the fall in temperature produced by p-OHA (3 micrograms, i.c.v.) and reduced that produced by p-OHN (3 micrograms, i.c.v.), respectively. The selective dopaminergic D1 receptor antagonist,
SCH 23390, and the D2 receptor antagonists,
sultopride and
metoclopramide, were without effect on the
hypothermia induced by either metabolite. Similarly,
amphetamine-
induced hypothermia was only inhibited by
haloperidol.
Apomorphine (0.1 mg kg-1, i.p.) did not potentiate the
hypothermia induced by either metabolite, whereas the selective dopaminergic D2 agonist,
quinpirole (0.2 mg kg-1, i.p.) did.
Amphetamine-
induced hypothermia was potentiated by
apomorphine and
quinpirole. 4. Neither the
5-hydroxytryptamine (5-HT) receptor blocker,
cyproheptadine, nor the
5-HT receptor agonist,
quipazine, modified metabolite-
induced hypothermia. In contrast,
amphetamine-
induced hypothermia was affected by these
5-HT drugs. 5. The
neuropeptide CCK-8 (0.04 mg kg-1, i.p.) and
gamma-butyrolactone (40 mg kg-1, i.p.) potentiated the
hypothermia produced by
amphetamine and its metabolites. Conversely,
desipramine (20 mg kg-1, i.p.) antagonized it.(ABSTRACT TRUNCATED AT 250 WORDS)