A comparison of the effects of 8-OH-DPAT pretreatment on different behavioural responses to 8-OH-DPAT

The effects of daily pretreatments with the prototypical 5-HT 1A receptor agonist 8-hydroxy-(di- n-propylamino) tetralin (8-OH-DPAT) (1.0 mg/kg s.c.) on behavioural responses to challenge by 8-OH-DPAT (0.5 mg/kg s.c.) due to activation of 5-HT 1A receptors were determined. The responses had strikingly different susceptibilities to pretreatment. These were not explicable by different effects on pre- and postsynaptic responses. Thus, two components of the 5-HT syndrome due to action at postsynaptic sites (i.e. flat body posture and reciprocal forepaw treading) were substantially attenuated 1 day after a single pretreatment with 8-OH-DPAT, but the tail-flick response, though due to action at postsynaptic 5-HT 1A sites, was completely unimpaired by 14 pretreatments while the hypothermic response which also probably involves postsynaptic sites showed progressively increased attenuation on 14 pretreatments. 8-OH-DPAT-induced hyperphagia which depends on activation of presynaptic sites was unimpaired by the pretreatment schedule. The results are discussed in relation to receptor reserve, second messenger changes and effects at NMDA receptors. They imply a need for caution in the use of chronic effects of 5-HTergic drugs on specific 5-HT 1A receptor-dependent responses as indices of mechanisms for the therapeutic actions of the drugs.