K. Bohmaker et al., COMPARATIVE EFFECTS OF CHRONIC 8-OH-DPAT, GEPIRONE AND IPSAPIRONE TREATMENT ON THE SENSITIVITY OF SOMATODENDRITIC 5-HT1A AUTORECEPTORS, Neuropharmacology, 32(6), 1993, pp. 527-534
Chronic treatment with the full 5-hydroxytryptamine1A (5-HT1A) agonist
8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), either by twice d
aily subcutaneous injection (0.2 or 2.0 mg/kg) or continuous subcutane
ous administration via osmotic minipumps (0.4 or 4.0 mg/kg/day), for 1
4 days, had no effect on the dose-response curves for inhibition of 5-
hydroxytryptophan (5-HTP) accumulation in rat cortex or hippocampus by
8-OH-DPAT or the partial 5-HT1A agonist BMY 7378. In contrast, chroni
c treatment with the nonbenzodiazepine putative anxiolytic gepirone vi
a osmotic minipumps (20 mg/kg/day) resulted in a small but significant
rightward shift (1.8-fold) in the dose-response curve to 8-OH-DPAT ch
allenge in the cortex and a slightly larger shift (2.4-fold) in the hi
ppocampus. Similarly, chronic treatment with another putative anxiolyt
ic, ipsapirone, administered via twice daily subcutaneous injections (
20 mg/kg), also resulted in a rightward shift (2.6-fold) in the dose-r
esponse curve to 8-OH-DPAT in the cortex and a slightly smaller shift
(2.3-fold) in the hippocampus. Neither drug, however, decreased the ma
ximal response. The present results are consistent with the suggestion
that the clinical anxiolytic effects of gepirone and ipsapirone, and
not of 8-OH-DPAT, may be related to their ability to desensitize somat
odendritic 5-HT1A autoreceptors; other potential mechanisms are discus
sed.