Decreased hypothalamic serotonin levels in adult rats treated neonatally with clomipramine

Pharmacol Biochem Behav. 1996 Dec;55(4):647-52. doi: 10.1016/s0091-3057(96)00276-6.


Early postnatal treatment with the antidepressant drug clomipramine has repeatedly been shown to lead to behavioural and physiological changes in adult rats. To provide some neurochemical correlates to these studies we have measured a number of monoaminergic parameters in the brains of adult (one year old) rats that were treated twice daily with 15 mg/kg clomipramine from postnatal day 2-14. The most consistent finding was that the hypothalamic levels of serotonin (5-HT) were decreased and those of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were increased in rats irrespectively whether they went through a range of behavioural and physiological tests or not. The numbers of beta-adrenoceptors in the frontal cortex and of alpha 2-adrenoceptors in the amygdala/piriform cortex were not changed. The decrease in hypothalamic 5-HT concentrations appears to be up to now the most consistent neurochemical alteration in adult rats that were neonatally treated with antidepressant drugs. It is, however, not clear what the relation is with the functional changes in these rats, that are proposed by some authors as an animal model for depression.

MeSH terms

  • Animals
  • Animals, Newborn / physiology*
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Biogenic Monoamines / metabolism
  • Chromatography, High Pressure Liquid
  • Clomipramine / pharmacology*
  • Depression, Chemical
  • Dopamine / metabolism
  • Female
  • Hypothalamus / drug effects
  • Hypothalamus / growth & development*
  • Hypothalamus / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic / drug effects
  • Serotonin / metabolism*


  • Antidepressive Agents, Tricyclic
  • Biogenic Monoamines
  • Receptors, Adrenergic
  • Serotonin
  • Clomipramine
  • Dopamine