Serotonergic mechanisms in the nucleus accumbens affected by chronic desipramine treatment.
The effects of repeated treatment of rats with desipramine on 5-HT mechanisms within the nucleus accumbens (NAS) have been studied in a functional model. Local microinjections of 5-HT, quipazine as well as 5-HT1A receptor agonist buspirone, 8-OH-DPAT and NDO-008, inhibited rat locomotor activity in the open-field test. The effect of 5-HT and buspirone was blocked by serotonergic receptor antagonists methysergide and cyanopindolol, respectively. Chronic, but not acute treatment of rats with desipramine (10 mg/kg, PO, twice a day for 21 days, tests were performed 24 h after the last dose) significantly attenuated behavioral depression after 5-HT and quipazine microinjections, while the effect of buspirone was left unchanged. On the basis of present data, it may be concluded that whereas both accumbens 5-HT1A and 5-HT2 receptors appear to be important to regulation of animals' motility, only 5-HT2 receptors seem to be the most likely targets of antidepressive treatment. These data, along with previously reported changes in limbic noradrenergic and dopaminergic activity after antidepressive treatment, may explain the energizing influence of drugs and electroconvulsive shocks on psychomotor retardation, a part of endogenous depression.
Płaźnik
A
A
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Stefański
R
R
Pałejko
W
W
Kostowski
W
W
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008784:Methysergide / Q000494:pharmacology; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D002839:Chromans; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C071048:3-propylamino-5-hydroxychroman; D012701:Serotonin; C047975:cyanopindolol; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D003891:Desipramine; D002065:Buspirone; D008784:Methysergide