Role of the D1 receptor for the dopamine agonist-induced one-trial behavioral sensitization of preweanling rats

Abstract

Rationale The neural mechanisms mediating the ontogeny of behavioral sensitization are poorly understood. Objective The purpose of the present study was to determine the role of the D1 receptor for the induction of dopamine agonist-induced behavioral sensitization during the preweanling period. Methods In the first experiment, the early ontogeny of NPA-induced behavioral sensitization was examined by pretreating male and female rats with saline or NPA (0.5, 1, or 2 mg/kg, IP) before placement in activity chambers on postnatal day (PD) 12, 16, 20, or 24. One day later, rats were tested with lower doses of NPA and the occurrence of locomotor sensitization was determined. In subsequent experiments, rats were injected with saline or the D1 receptor antagonist SCH23390 (0.1, 0.5, 1, or 5 mg/kg, IP) 0, 15, 30, or 60 min before cocaine, methamphetamine (METH), or NPA pretreatment. The next day, rats were tested with the same dopamine agonist again and sensitized responding was assessed. Results NPA produced one-trial behavioral sensitization at all ages tested. In preweanling rats, SCH23390, regardless of dose, was ineffective at preventing the induction of cocaine-, METH-, or NPA-induced one-trial behavioral sensitization. Conclusions The present results are in partial contrast to adult rodent studies, in which SCH23390 blocks the induction of METH- and apomorphine-induced behavioral sensitization, but not cocaine sensitization. When these findings are considered together, it appears that D1 receptor stimulation is not necessary for the induction of behavioral sensitization during the preweanling period, although D1 receptors may play a more important role in adulthood.

Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats

“…Using a one-trial protocol, researchers testing adult rats and mice have reported that D1 (Fontana et al 1993; Valjent et al 2010) and D2 receptor antagonists (Weiss et al 1989; Fontana et al 1993) block psychostimulant-induced behavioral sensitization. Conversely, neither D1 nor D2 receptor antagonists prevent the induction of methamphetamine sensitization in preweanling rats (present study; Mohd-Yusof et al 2014). This pattern of results suggests that the neural mechanisms underlying the induction of behavioral sensitization, perhaps including the availability of ‘redundant pathways’, differs between early ontogeny and adulthood.…”

“…In terms of the present study, it is also possible that redundant pathways, perhaps involving the 5-HT or adrenergic system, may mediate the induction of one-trial behavioral sensitization in preweanling rats. Such redundant pathways would explain why neither SCH23390 (Mohd-Yusof et al 2015) nor raclopride (present study) blocked the initial induction of methamphetamine-induced one-trial behavioral sensitization in preweanling rats. On first appraisal, methamphetamine’s mechanism of action and selectivity at monoamine transporters may seem to argue against a ‘redundant pathway’ explanation.…”

“…A different pattern of effects was observed when using a one-trial procedure, as D2 or D1/D2 receptor antagonism did not prevent the induction of methamphetamine-induced behavioral sensitization. These results suggest that the neural mechanisms mediating the initial induction of behavioral sensitization in young rats differ depending on whether a one-trial or multi-trial procedure is used (see also Mohd-Yusof et al 2014). Consistent with this possibility, researchers using adult rodent models have proposed that one-trial and multi-trial behavioral sensitization varies in terms of second messenger signaling mechanisms, associative learning factors, and the role of DA receptors (Fontana et al 1993; White et al 1998; Battisti et al 2000; Valjent et al 2010).…”

“…In a separate experiment, a one-trial procedure was conducted as just described, with the exception that rats were injected with D1 and/or D2 receptor antagonists in their home cage on PD 13–15. This general methodology (i.e., administering antagonists 15 min prior to DA agonist treatment and testing rats 24 hr later) is similar to studies reported by Fontana et al (1993) and Mohd-Yusof et al (2014). Lower doses of DA agonists were administered on the test day, relative to the pretreatment day, in order to preferentially induce locomotor activity rather than stereotypy (for a fuller discussion, see Robinson and Becker 1986).…”

“…Few studies have examined the receptor systems mediating behavioral sensitization in preweanling rats (for an exception, see Duke et al 1997), but those that have report some interesting ontogenetic differences. For example, pretreatment with the D1 receptor antagonist SCH23390 does not prevent the methamphetamine- or cocaine-induced one-trial behavioral sensitization of preweanling rats (Mohd-Yusof et al 2014); whereas, SCH23390 blocks the one-trial behavioral sensitization of cocaine-treated adults (Fontana et al 1993; Valjent et al 2010). The importance of the D2 receptor for the one-trial and multi-trial behavioral sensitization of preweanling rats has not been assessed.…”