Studies on the neuronal circuits involved in the discriminative stimulus effects of 5-hydroxytryptamine1A receptor agonists in the rat.
Rats were trained to discriminate 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.1 mg/kg i.p.) or 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT, 1.25 mg/kg i.p.), a selective and nonselective 5-hydroxytryptamine1A (5-HT, serotonin) receptor agonist, respectively, from saline in a two-lever procedure. The selective 5-HT1A receptor agonist ipsapirone substituted completely for 8-OH-DPAT (ED50, 1.52 mg/kg) and 5-OMe-DMT substituted partially for 8-OH-DPAT, whereas 8-OH-DPAT (ED50, 0.07 mg/kg) and ipsapirone (ED50, 4.15 mg/kg) substituted completely for 5-OMe-DMT. These results suggest that the discriminative stimulus properties of both 8-OH-DPAT and 5-OMe-DMT are 5-HT1A receptor mediated, although 5-OMe-DMT may involve an additional interaction with other 5-HT receptor subtypes. 5-OMe-DMT substituted for 8-OH-DPAT after application in the lateral ventricle (ED50, 3.0 micrograms/rat) and the dorsal raphe nucleus (DRN, 1.1 micrograms/rat). After application in the DRN (ED50 range, 1.4-5.0 micrograms/rat) and the median raphe nucleus (2.3 micrograms/rat), and after bilateral application into the CA-4 region of the dorsal hippocampus (4.1 micrograms/rat), 8-OH-DPAT also produced responding on the 8-OH-DPAT lever. Ipsapirone also substituted for 8-OH-DPAT after application into the DRN and the hippocampus (ED50S, 38 and 62 micrograms/rat, respectively). The 5-HT1A mixed agonist-antagonist (1-(2-methoxyphenyl) 4-[4-(2-pthalimido)butyl]piperazine, i.p. NAN-190) attenuated the discriminative stimulus effects of 8-OH-DPAT injected i.p. (0.1 mg/kg), into the DRN (10 micrograms) or into the hippocampus (2 x 10 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychopharmacology, Troponwerke Cologne, F.R.G.
R
R
Schreiber
J
J
de Vry
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*
D008732:Methoxydimethyltryptamines; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin