Effects of 5-HT1A receptor ligands on a safety signal withdrawal procedure of conflict in the rat

Effects of 5-HT 1A receptor agonists, partial agonists and a silent antagonist on the performance of the conditioned emotional response test in the rat

“…In contrast to the data obtained in these ethological models of anxiety, Charrier et al (1994) failed to observe an anxiolyticlike action of WAY-100135 in the safety signal withdrawal conflict procedure in the rat. Perhaps the most straightforward explanation for the discrepancy between the results from these various studies is due to differences in the models used.…”

“…In models involving innate behaviours such as the light /dark box and the elevated plus maze, results have been extremely variable with the demonstration of anxiolytic, anxiogenic or no effects of 5-HT 1A receptor partial agonists (Dourish 1987;Treit 1991;Wilkinson and Dourish 1991). The effects of 5-HT 1A receptor ligands in animal models of anxiety using either conflict procedures (eg., Geller and Seifter 1960;Vogel et al 1971) or the CER procedure (Estes and Skinner 1941; for a review see Davis 1990) have also proved inconsistent (Barrett and Witkin, 1991;Barrett and Vanover 1993), however, a number of authors have reported that 5-HT 1A receptor partial agonists have anxiolytic effects in such tests (Schefke et al 1989;Sanger 1990Sanger , 1992Barrett and Witkin, 1991;Charrier et al 1994). Although colleagues (1991, 1993) argue that the most consistent anxiolytic-like effects of 5-HT 1A receptor partial agonists are observed in conflict tests in pigeons, Sanger (1990Sanger ( , 1992, reported robust anxiolytic-like effects with ipsapirone in the CER test in the rat (see also Rittenhouse et al 1992).…”

Comparative effects of novel 5-HT 1A receptor ligands, LY293284, LY315712 and LY297996, on plus-maze anxiety in mice

“…([) pindolol, pindobind 5-HT 1A , SDZ 216525, WAY 100635 and p-MPPI (Cao and Rodgers 1997a,b,c). However, they contrast with the general lack of e¤ect of 5-HT 1A receptor antagonists in the rat Vogel (Moreau et al 1992;Przegalinski et al 1995), Geller-Seifter (Charrier et al 1994;Cervo and Samanin 1995), conditioned emotional response , shock-induced ultrasonic vocalisation (Maurel Remy et al 1996), social interaction (Cadogan et al 1994;File et al 1996) and plus-maze (Bickerdike et al 1995;Collinson and Dawson 1996;File et al 1996) procedures. The potential importance of species to the behavioural e¤ects of 5-HT 1A receptor antagonists is further suggested by the anxiolytic-like activity of (S)-WAY 100135 and WAY 100635 in the mouse plus-maze (Rodgers and Cole 1994b;Cao and Rodgers 1997c) and the mouse light / dark exploration Fletcher et al 1996) tests.…”

“…Furthermore, although 5-HT 1A receptor antagonists are generally inactive in procedures based upon conditioned responses (e.g. Moreau et al 1992;Charrier et al 1994;Cervo and Samanin 1995;Przegalinski et al 1995;Maurel Remy et al 1996;Stanhope and Dourish 1996), more positive results have been reported in unconditioned models (e.g. Moreau et al 1992;Bell and Hobson 1993a,b;Njunge et al 1993;Sanchez 1993Sanchez , 1995Lopez-Rubaclava and Fernandez-Guasti 1994;Przegalinski et al 1994Przegalinski et al , 1995Shepherd et al 1994).…”

Anxiolytic-like profile of p -MPPI, a novel 5HT 1A receptor antagonist, in the murine elevated plus-maze

“…For example, (S)-UH-301, the S-enantiomer of the 5-fluoro analogue of 8-OH-DPAT with antagonistic effects at both pre-and post-synaptic 5-HT 1A receptors (Bjork et al 1991), has been found to have anxiolytic-like effects in the mouse light-dark and rat elevated plus-maze tests but to lack activity in traditional conflict procedures (Moreau et al 1992). Furthermore, although the 5-HT 1A antagonist, WAY 100135, has been reported to have anxiolytic effects in the rat potentiated startle model (Fletcher et al 1992), as well as mouse light-dark (Bill and Fletcher 1994), elevated plus-maze (Rodgers and Cole 1994b) paradigms, negative findings have also been obtained (Cadogan et al 1994;Charrier et al 1994;Bickerdike et al 1995;Cervo and Samanin 1995;Przegalinski et al 1995). While some of these negative reports may be due to the use of limited dose ranges, it is pertinent that the affinity of (S)-UH-301 for 5-HT 1A sites is only 8-fold higher than its affinity for dopamine D 2 receptor where it is reported to have agonist effects (Bjork et al 1991) while, at certain doses, WAY 100135 has been found to decrease raphe firing, an action perhaps related either to residual 5-HT 1A receptor partial agonist activity or 1 -adrenoceptor antagonism (Routledge 1996).…”