Long-term imipramine effects are prevented by NMDA receptor blockade.
Long-term exposure to different antidepressant treatments induces increased motor response to central stimulants, due to a selective supersensitivity of dopamine D2 receptors in the limbic areas. Such an effect is accompanied by down-regulation of dopamine D1 receptor number, and by a decreased response of adenylyl cyclase to dopamine stimulation in the limbic system. Moreover, the number of beta-adrenergic receptors and the response of adenylyl cyclase to beta-adrenergic stimulation in the cortex result to be reduced. The present data confirms that imipramine (10 mg/kg twice a day for 3 weeks) produces such effects, and shows that the co-administration of imipramine with MK-801 (administered by a subcutaneously implanted osmotic minipump delivering 0.05 mg/kg/day of the compound) prevented the occurrence of both the behavioral supersensitivity to quinpirole, and the decrease of dopamine D1 and beta-adrenergic receptor function.
De Montis
M G
MG
Institute of Pharmacology, University of Siena, Italy.
Gambarana
C
C
Meloni
D
D
Taddei
I
I
Tagliamonte
A
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D007099:Imipramine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
D015259:Dopamine Agents; D004873:Ergolines; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D019257:Quinpirole; D016291:Dizocilpine Maleate; D007099:Imipramine