Response suppression in rats after bilateral microinjection of 5-hydroxytryptophan in lateral hypothalamus

Joseph N. Hingtgen, Anantha Shekhar, Joseph A. DiMicco, M. H. Aprison

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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.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalBiological psychiatry
Issue number7
StatePublished - Apr 1 1988


ASJC Scopus subject areas

  • Biological Psychiatry

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