Acute stimulation of 5-HT1A receptors has been reported to diminish some 5-HT2 receptor-mediated responses in the rat, but there is controversy as to whether repeated stimulation of 5-HT1A receptors leads to identical changes. In this study, we tested the influence of repeated treatment with the
5-HT1A receptor agonist
ipsapirone (0.5 g/l in
drinking water for 21 days) on some 5-HT2 receptor-mediated responses elicited by the acute injection of the 5-HT1C/5-HT2 receptor agonist
1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). These responses included
hyperglycemia,
corticosterone release, and head shakes; cortical 5-HT2 receptor number and DOI-induced
prolactin release (a 5-HT1C/5-HT2 receptor-mediated event) were also analyzed. In a first series of experiments,
ipsapirone administration for 1, 8, 15, and 20 days reduced the duration fo
shock-induced ultrasonic vocalization.
Ipsapirone administration for 21 days reduced fluid intake and decreased
body weight, but did not affect baseline plasma
glucose,
corticosterone, and
prolactin levels or cortical 5-HT2 receptor number. The increases in plasma
glucose levels elicited by acute injection of either DOI (0.1-1 mg/kg i.v.) or
clonidine (an alpha 2-
adrenoceptor agonist; 0.05 mg/kg i.v.) were reduced in
ipsapirone-pretreated rats. The maximal effects of DOI and
clonidine on plasma
corticosterone or
prolactin levels were not affected by
ipsapirone pretreatment.
Ipsapirone decreased the area under the
corticosterone curve in both DOI- and
clonidine-treated rats. Lastly, the head-shake response to DOI (0.5-2 mg/kg s.c.) was similar in vehicle- and
ipsapirone-pretreated rats. These data indicate that a 3-week treatment with
anxiolytic doses of the
5-HT1A receptor agonist
ipsapirone does not desensitize 5-HT2 receptors.