Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat

Abstract

Colpaert, F.C.: Effects of putative a-adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat. Drug Dev. Res. 7:125-140, 1986. lntraperitoneal injection of 20 mg/kg of xylazine causes loss of the righting reflex (LRR) and exophthalmia in the rat. The experiments determined some of the pharmacological characteristics of these responses to xylazine. The putative a2-adrenoceptor antagonists yohimbine, piperoxan, CGS 7525 A, and idazoxan blocked the LRR response; tolazoline, phentolamine, and salbutamol attenuated the response to some extent, whereas prazosin, aceperone, and phenoxybenzamine exerted no apparent effect. The putative a2-agonists clonidine, guanabenz, guanfacine, guanoxabenz, tiamenidine, and naphazoline were identified in an earlier study as acting only as partial agonists in depressing rat behavior and were found here to antagonize partially the LRR response. Other compounds that attenuated but did not block the response either have some affinity for and perhaps act as partial antagonists at a2-receptors (e.g., phentolamine, LSD, lisuride) or exert some arousing or behaviorally stimulating action (e.g., cocaine, nomifensine, tranylcypromine, apomorphine). Arousing sensory stimulation also produced a partial attenuation of the LRR response. The xylazine-induced exophthalmia appeared responsive to the putative alantagonists prazosin and aceperone, and other drugs exerting al-antagonist activity also antagonized the exophthalmia. The doses at which compounds antagonize xylazineReceived final version September 11, 1985; accepted September 12, 1985 Address reprint requests to Dr. F.C. Colpaert, Department of Psychopharmacology, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. 0 1986 Alan R. Liss, Inc. 126Colpaert induced LRR and exophthalmia in rat might offer an estimate of the compounds' in vivo potency in acting as antagonists at a2-and a,-adrenoceptors, respectively.

Effects of Acute and Subchronic Administration of Dexefaroxan, an α2-Adrenoceptor Antagonist, on Memory Performance in Young Adult and Aged Rodents

“…The bell shape of the dose-response curves and the same peak effective dose of dexefaroxan reported in this study was observed also on cortical acetylcholine outflow, as measured in vivo by microdialysis in the rat (Tellez et al, 1997), and on circling behavior in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway (Chopin et al, 1999). Bell-shaped dose-response curves have also been reported for the ␣ 2 -adrenoceptor antagonists idazoxan and yohimbine in reversing the loss of the righting reflex in behavioral studies (Colpaert, 1986), and on cortical high-voltage spindles in electroencephalogram studies (Yavich et al, 1994). Although the inverted U-shape of the dose-response curve has been attributed to partial agonist actions at ␣ 2 -adrenoceptors (Colpaert, 1986) and to actions at non␣ 2 -receptors (Yavich et al, 1994), the precise mechanisms underlying this phenomenon are not known for certain.…”

“…Bell-shaped dose-response curves have also been reported for the ␣ 2 -adrenoceptor antagonists idazoxan and yohimbine in reversing the loss of the righting reflex in behavioral studies (Colpaert, 1986), and on cortical high-voltage spindles in electroencephalogram studies (Yavich et al, 1994). Although the inverted U-shape of the dose-response curve has been attributed to partial agonist actions at ␣ 2 -adrenoceptors (Colpaert, 1986) and to actions at non␣ 2 -receptors (Yavich et al, 1994), the precise mechanisms underlying this phenomenon are not known for certain.…”

The ?2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats

“…This compound blocks the pharmacological effects of ~2-adrenoceptor agonists such as clonidine and xylazine but has not been found to be active in most tests used for selecting antidepressant drugs (Dettmar et al 1983;Doxey et al 1983;Colpaert and Janssen 1985;Colpaert 1986). However, there are relatively few reports concerned with the behavioural actions of idazoxan.…”

In vivo pharmacological activity of r 47 243 in rat: A comparison with putative α2‐adrenoceptor antagonists

“…The data presented here indicate that subcutaneous injection of R 47 243 causes a dose-dependent antagonism of the LRR; a full blockade (i.e., LRR scores 0) was obtained at 2.9 (1.7-5.0) mg/kg. Previous work [Colpaert 1985b; see also Hsu, 19811 has shown that subcutaneous injection of a2-antagonists, and only that of a2-antagonists, produces a complete blockade of the LRR response to xylazine in rats. The present data thus suggest that, according to this behavioral definition, R 47 243 acts as an a2-antagonist in rats.…”