Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats.
We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)
Lang
A
A
Institute of Physiology, Tartu University, Estonia.
Harro
J
J
Soosaar
A
A
Kõks
S
S
Volke
V
V
Oreland
L
L
Bourin
M
M
Vasar
E
E
Bradwejn
J
J
Männistö
P T
PT
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D020109:Devazepide; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010671:Phenylurea Compounds; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; C058121:L 365260; D016291:Dizocilpine Maleate; D003024:Clozapine; D006220:Haloperidol; D020109:Devazepide; D001058:Apomorphine