Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats

Abstract

Colpaert, F.C.:Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats. Drug Dev. Res. 9:125-131, 1986. Nine rats were trained to discriminate 10 mglkg of cocaine HCI from saline in a two-lever food-reinforced drug discrimination procedure. Saline and 0.31-10 mglkg doses of cocaine were tested for generalization after pretreatment with either vehicle or 0.04 and 0.16 mgl kg of haloperidol. The 0.04 and 0.16 mg/kg doses of haloperidol produced a 2.3 and 5.0-fold shift to the right, respectively, of the cocaine generalization gradient. Extrapolation of the generalization data suggests that about 3 mg/kg of haloperidol is required to antagonize completely the discriminative effects of the 10 mg/kg training dose of cocaine. Cocaine (0.63 mglkg) reversed the rate-depressant effects of 0.04 mglkg of haloperidol, but even 10 mglkg only partially attenuated the behavioral depression produced by 0.16 mglkg of haloperidol. Also, up to 10 mg/kg doses of cocaine exerted no reliable effect on the alternative lever responding produced by 0.04 or 0.16 mg/kg of haloperidol. The data suggest that a 2.3-5.0-fold shift of the cocaine gradient, but not a complete blockade of the discriminative effects of the 10 mglkg training dose of cocaine, can be achieved with doses of haloperidol at which the drug presumably interacts in a specific manner with dopamine receptors in the brain.

Pharmacological validation of ritanserin and risperidone in the drug discrimination test procedure in the rat

“…The partial antagonism of the discriminative stimulus properties of cocaine with risperidone confirms earlier results indicating that even high doses of DA-antagonists are unable to completely block the 10.00 mgikg cocaine cue [Cunningham and Appel, 1982;Colpaert, 19861. These results thus confirm the idea that the discriminative stimulus properties of cocaine only partially depend upon a dopamine stimulatory activity [Colpaert, 1986;Colpaert et al, 1979Colpaert et al, , 1980Snoddy and Tessel, 19831. The inactivity of risperidone at doses up to 0.63 mgikg on both the xylazine-and the 8-OHDPAT-cue indicates risperidone to have no strong in vivo interactions with a,-adrenoceptor and serotonin 5-HT,, mechanisms.…”

“…Because in the drug discrimination test procedure only drugs producing analogous subjective effects as the training drug reveal a stimulus generalization with the training drug [Colpaert and Slangen, 19821, the present results indicate ritanserin and risperidone to be devoid of the subjective effects analogous to LSD, %OHPAT, d-amphetamine, cocaine, chlordiazepoxide, xylazine, and fentanyl. Thus, both ritanserin and risperidone possess no intrinsic hallucinogenic [Glennon and Rosecrans, 1982;Glennon et al, 19831, no serotonin 5-HT,,-agonist [Glennon, 1986;Tricklebanck et al, 19871, no stimulatory and/or dopaminergic [Nielsen et al, 1989;Colpaert, 1986;Colpaert et al, 1978a,b], no benzodiazepine-like [Colpaert et al, 1976a;Sanger and Zivkoviv, 19871, no a2-adrenoceptor agonist [Colpaert and Janssen, 198.51 nor central opiate-like [Colpaert, 1978;Colpaert and Janssen, 19861 effects. The lack of stimulus generalization with ritanserin and risperidone to any of the training conditions was also re- flected in the nearly perfect FRF-values ( 5 11 .OO) and percentages of responding on the selected saline lever (>97%).…”