Operant response suppression induced with systemic administration of 5-hydroxytryptophan is centrally mediated.
Intracerebroventricular (ICV) administration of selective serotonergic agents was used to examine the extent of central mediation of 5-HTP-induced operant response suppression in rats. ICV administration of LY53857 (1.0, 3.75, or 7.5 micrograms/5 microliters/5 min) dose dependently blocked response suppression induced with systemically administered 5-HTP (25 mg/kg, IP), whereas ICV 0.9% saline (5 microliters over 5 min) had no significant effect on 5-HTP-induced response suppression. ICV ketanserin (7.5 micrograms/5 microliters/5 min) also blocked response suppression induced with systemically administered 5-HTP. ICV administration of the 5-HT2A/2C receptor agonist DOI (80 micrograms/5 microliters/5 min) induced significant periods of response suppression in this model, which was blocked with LY53857 (1.0 mg/kg, IP) pretreatment. These data demonstrate that central administration of 5-HT2A/2C antagonists potently attenuate operant response suppression induced with systemically administered 5-HTP or DOI and are in agreement with previous findings suggesting central mediation of 5-HTP-induced operant response suppression.
Engleman
E A
EA
Indiana University School of Medicine, Department of Psychiatry, Indianapolis, USA.
Murphy
J M
JM
Zhou
F C
FC
Aprison
M H
MH
Hingtgen
J N
JN
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D017933:Peripheral Nervous System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013238:Stereotaxic Techniques
D000662:Amphetamines; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D006916:5-Hydroxytryptophan; C032663:LY 53857; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine