Functional reactivity of the dopaminergic system following acute and chronic ketamine treatments.
This study examined the effects of acute (15 mg/kg, i.p.) and chronic subanesthetic (15 mg/kg, i.p., t.i.d, for 6 days) doses of ketamine [a noncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist] on amphetamine (presynaptic dopamine releasing agent; 10 mg/kg, i.p.) and apomorphine (a D(2) receptor agonist; 1 mg/kg, i.p.)-induced stereotyped behaviors. The effect of acute and chronic ketamine on haloperidol (a D(2) receptor antagonist; 1.6 mg/kg, i.p.)-induced catalepsy was also examined. Acute ketamine and chronic ketamine pretreatment increased amphetamine-induced stereotyped sniffing and locomotion compared with control groups. Acute ketamine significantly increased apomorphine-induced stereotyped sniffing. However, chronic ketamine had no significant effect on apomorphine-induced stereotyped sniffing. Acute, but not chronic ketamine treatment abolished haloperidol-induced catalepsy. The increase in amphetamine-induced stereotyped behaviors and the reversal of haloperidol-induced catalepsy by acute ketamine suggest that blockade of NMDA receptors by ketamine facilitates dopaminergic transmission. The absence of significant effect of chronic ketamine on apomorphine-induced stereotyped sniffing and haloperidol-induced catalepsy suggests that chronic ketamine does not modulate postsynaptic dopaminergic D(2) receptors. It is suggested that chronic ketamine increased amphetamine-induced behaviors by causing hypersensitivity of presynaptic dopamine releasing mechanisms on dopaminergic terminals.
Owolabi
A R
AR
Department of Physiological Sciences and Department of Pharmacology, Obafemi Awolowo University, Ile-Ife, Nigeria.
Akanmu
M A
MA
Ukponmwan
O E
OE
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D017448:Receptors, Dopamine D2; D007649:Ketamine; D000661:Amphetamine; D006220:Haloperidol; D001058:Apomorphine