Excitatory and inhibitory behavioral responses to the pharmacological stimulation of serotonergic function in dorsalis raphe lesioned rats.
Neurotoxin-induced lesions of 5-HT neurons produce supersensitivity of 5-HT1 receptors without affecting 5-HT2 receptor binding in the brain. This model was used in the present work to analyze the role of 5-HT receptor subtypes in the mechanism controlling the excitatory and inhibitory behavioral responses to the pharmacological stimulation of 5-HT systems. Dorsalis raphe (DR) lesions were made by stereotaxic injection of kainic acid. At day 30 after injection DR-and control rats displayed similar baseline behavior in hole board tests. Three days later DR-and control rats received an ip injection of fluoxetine (5 or 10 mg/kg) 30 min before injecting ip 5-HTP(15 or 30 mg/kg). Immediately before and after each ip injection the excitatory response (myoclonic syndrome) was evaluated. DR-and control-group showed similar scores of myoclonus in response to fluoxetine-5-HTP. The inhibitory response was investigated in hole board trials performed 30 min after the second ip injection. The DR lesion potentiated the behavioral depressive effect of fluoxetine-5-HTP. In agreement with data in the literature the DR lesion caused 74.9% loss of forebrain 5-HT and 75% increases of 3H-5HT binding in cortex membranes. Most components of the excitatory response, which remained unchanged in the DR-lesioned rats, might be related to 5-HT2 receptors. The increased inhibitory response to 5-HT stimulation in DR-lesioned rats would be due to the supersensitivity of 5-HT1 receptors.
Rodríguez Echandía
E L
EL
Laboratorio de Investigaciones Cerebrales (LINCE-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
González
A S
AS
Fóscolo
M R
MR
Broitman
S T
ST
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005473:Fluoxetine / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D005473:Fluoxetine; D007608:Kainic Acid