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Discriminative stimulus properties of /+/-oxaprotiline in rat

100%

Filip M. , Chojnacka-Wojcik E. , Przegalinski E.

Polish Journal of Pharmacology

1993

tom 45

nr 2

151-156

Using a drug discrimination procedure on a fixed ratio (FR) 10 schedule of reinforcement, rats were trained to distinguish between the stimulus properties of the selective inhibitor of noradrenaline uptake (+)-oxaprotiline ((+)-OXA) and saline. Fifty per cent of the rats that learned to reliably discriminate (+)-OXA from saline, reached high discrimination accuracy. In substitution testing, maprotiline (MAP) and desipramine (DMI) produced dose-related responding on the (+)-OXA lever. (-)-OXA failed to show substitution. The results of our findings demonstrate that (+)-OXA may be used as a discriminative cue in rats. The NA uptake inhibition seems to be involved in the effect of this drug.

Antagonism of the discriminative stimulus properties of cocaine with the combination of a dopamine D1 and D2 antagonist

80%

Meert T. F. , De H. P. , Aerts N. , Clincke G.

1996

tom 56

nr 4

897-905

Antagonism of the discriminative stimulus properties of 10 mg/kg cocaine was studied in rats by use of the dopamine D1 antagonist SCH 23390 and the D2 antagonist haloperidol. Whereas SCH 23390 and haloperidol were by themselves unable to antagonize the cueing properties of cocaine, the combination of both dopamine antagonists resulted in a complete blockade of the cocaine cue. In the presence of a fixed dose of 0.01 and 0.04 mg/kg haloperidol, the EDS50's (it is the effective dose in 50% of the animals) of SCH 23390 for cocaine antagonism were 0.043 and 0.012 mg/kg, respectively. Similarly, the EDS50's of haloperidol in combination with 0.01 and 0.04 mg/kg SCH 23390 were 0.021 and 0.024 mg/kg. The combined treatment of haloperidol and SCH 23390 resulted in strong response-rate reductions. At all combination regimens resulting in a complete blockade of the cocaine cue, response rate was reduced to less than 20% of the control values. These results indicate that the cueing properties of cocaine are both dopamine D1- and D2-mediated and that a combined antagonism of both receptor subtypes can lead to a complete antagonism of the cueing properties of cocaine which is associated with severe attenuation of response rate.