Effects of daily SKF 38393, quinpirole, and SCH 23390 treatments on locomotor activity and subsequent sensitivity to apomorphine

Abstract

In three experiments, male Wistar rats (250-350 g) were injected (SC) daily with the D1-type dopamine receptor agonist, SKF 38393 (0.0, 4.0, 8.0, or 16.0 mg/kg), the D2-type dopamine receptor agonist, quinpirole (0.0, 0.3, or 3.0 mg/kg), and/or the D1-type dopamine receptor antagonist, SCH 23390 (0.0 or 0.5 mg/kg) for 8-10 days. After each daily injection, the rats were tested for locomotor activity in photocell arenas for 20 min. Following this subchronic pretreatment, all rats were challenged with the mixed dopamine receptor agonist apomorphine (1.0 mg/kg, SC) and tested for locomotor activity. SKF 38393 treatments produced a dose-dependent decrease in locomotor activity which did not significantly change across days. Quinpirole also depressed locomotor activity when first injected, but this quinpirole-induced inhibition of activity progressively decreased across days. When subsequently challenged with apomorphine, rats in both the SKF 38393 and the quinpirole pretreatment groups displayed greater locomotor activity than rats pretreated with only vehicle. Although SCH 23390 pretreatments did not affect subsequent sensitivity to apomorphine, SCH 23390 completely blocked the effect of quinpirole. These results suggest that although repeated D1 receptor stimulation may be sufficient to induce behavioral sensitization to apomorphine, D2 receptor stimulation also contributes to the effect.

Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine

“…As noted previously, rats sensitized to quinpirole display cross-sensitization to cocaine and apomorphine (Horger and Schenk 1991;Mattingly et al 1993), and cross-sensitization between cocaine and apomorphine has also been reported (Kityakin 1994). The lack of cross-sensitization between 7-OH-DPAT and apomorphine and cocaine may be related to the apparent inability of repeated 7-OH-DPAT treatments to induce autoreceptor subsensitivity.…”

“…Indeed, even doses of 7-OH-DPAT that acutely decreased dopamine synthesis did not significantly affect basal dopamine synthesis with repeated administration. Thus, the development of behavioral sensitization to high doses of 7-OH-DPAT, like tolerance to the initial locomotor inhibition, does not appear to be Bannon et al 1980;Brown et al 1985;Horger and Schenk 1991;Hoffman and Wise 1993;Kiyatkin 1994;Mattingly et al 1993;Rowlett et al 1991Rowlett et al , 1993Rowlett et al , 1995Szechtman et al 1994 related to changes in autoreceptor sensitivity. Interestingly, it has recently been reported that rats sensitized to the locomotor-activating effects of the D2-type agonist, bromocryptine, like 7-OH-DPAT, are not crosssensitized to cocaine (Hoffman and Wise 1993).…”

“…As mentioned, this pattern of activity changes is similar to that produced by quinpirole when short duration activity test intervals are used (cf. Mattingly et al 1993;Rowlett et al 1995). With longer test intervals, however, quinpirole has been reported to produce a biphasic locomotor response acutely and locomotor sensitization with repeated treatment Szechtman et al 1994).…”

“…This lack of change in the sensitivity of autoreceptors with repeated 7-OH-DPAT treatment may account for the differential effect of repeated quinpirole and 7-OH-DPAT treatments on subsequent sensitivity to apomorphine (cf. Mattingly et al 1993; expt 1). The development of autoreceptor subsensitivity has also been suggested to be one of several mechanisms mediating the development of behavioral sensitization to the indirect agonist, cocaine (see Henry et al 1989).…”

“…This pattern of activity observed with repeated 7-OH-DPAT treatments is almost identical to that observed previously with repeated quinpirole treatments under the same test conditions (cf. Mattingly et al 1993). However, repeated quinpirole treatments significantly increase the locomotor response to a subsequent apomorphine (1.0 mg/kg) challenge injection , whereas repeated 7-OH-DPAT treatments in expt 1 did not affect subsequent behavioral sensitivity to the same challenge dose of apomorphine.…”