Response suppression in rats after bilateral microinjection of 5-hydroxytryptophan in lateral hypothalamus.
Studies using the 5-hydroxytryptophan (5-HTP) animal model of depression have led to the development of the hypersensitive postsynaptic serotonin receptor theory of depression. To demonstrate more clearly that the 5-HTP-induced suppression is a centrally mediated phenomenon, rats were implanted with bilateral cannulae in the lateral hypothalamus and received microinjections of D,L-5-HTP (100-500 ng) 15 min after the start of a VI operant session (milk reinforcement). Significant decreases in responding were observed that were comparable to those obtained after a systemic injection of 50 mg/kg D,L-5-HTP. Rats receiving a microinjection of 5-HTP in the posterior hypothalamus did not exhibit a behavioral effect. Rats working on shock-avoidance schedules did not demonstrate response suppression following microinjection of 5-HTP into the lateral hypothalamus, which is the same result as that following systemic 5-HTP administration. These data support the important role previously assigned to central 5-HT mechanisms in the 5-HTP animal model of depression.
Hingtgen
J N
JN
Section of Applied and Theoretical Neurobiology, Indiana University School of Medicine, Indianapolis 46223.
Shekhar
A
A
DiMicco
J A
JA
Aprison
M H
MH
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007026:Hypothalamic Area, Lateral / Q000187:drug effects*; D007267:Injections; D008297:Male; D009042:Motivation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D011985:Receptors, Serotonin; D006916:5-Hydroxytryptophan