Increase in number of LHRH neurones in septal-preoptic area of rats following chronic amitriptyline treatment: implication in antidepressant effect.
Recent studies have implicated the peptide LHRH in a variety of actions including a role in modulation of affective behavior. The present study has been undertaken to determine its involvement in the action of antidepressants, if any, using amitriptyline (AMT) as the model antidepressant drug. The repeated administration of AMT (10 mg/kg/day) in rats increased the number of LHRH neurones in the septal-preoptic area. While 1 week of AMT treatment slightly augmented the number of LHRH neurones, the rise was not statistically significant, however, following 2 weeks of AMT treatment, a significant (P < 0.05) increase (41.05%) was observed. Three and four weeks of AMT treatment further increased the number of neurones by 60.84% and 72.96% respectively; a remarkable rise in the LHRH immunoreactivity around organum vasculosum of lamina terminalis (OVLT) was also noticed. Acute AMT treatment had no effect on the number of neurons; however, the intensity of immunoreaction in the OVLT was slightly decreased. In the behavior despair test, a single dose of AMT displayed an immobility reducing effect which was also shown by a single dose of LHRH (1 mg/kg). The combination of LHRH (1 mg/kg) and AMT also reduced the immobility; the effect was the same as one produced by each drug given separately. The results suggest that chronic AMT treatment may induce transcription and translation in LHRH cells and that the peptide LHRH may be involved in the mediation of the antidepressant effect, characteristic of AMT.
Jain
M R
MR
Department of Pharmaceutical Sciences, Nagpur University, India.
Subhedar
N K
NK
D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003863:Depression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000639:Amitriptyline; D007987:Gonadotropin-Releasing Hormone