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

Abstract

Rationale There is suggestive evidence that the neural mechanisms mediating one-trial and multi-trial behavioral sensitization differ, especially when the effects of various classes of dopamine (DA) agonists are examined. Objective The purpose of the present study was to determine the role of the D2 receptor for the induction of one-trial and multi-trial methamphetamine sensitization in preweanling rats. Methods In a series of experiments, rats were injected with saline or raclopride (a selective D2 receptor antagonist), either alone or in combination with SCH23390 (a selective D1 receptor antagonist), 15 min prior to treatment with the indirect DA agonist methamphetamine. Acute control groups were given two injections of saline. This pretreatment regimen occurred on either postnatal days (PD) 13–16 (multi-trial) or PD 16 (one-trial). On PD 17, rats were challenged with methamphetamine and locomotor sensitization was determined. Results Blockade of D2 or D1/D2 receptors reduced or prevented, respectively, the induction of multi-trial methamphetamine sensitization in young rats, while the same manipulations had minimal effects on one-trial behavioral sensitization. Conclusions DA antagonist treatment differentially affected the methamphetamine-induced sensitized responding of preweanling rats depending on whether a one-trial or multi-trial procedure was used. The basis for this effect is uncertain, but there was some evidence that repeated DA antagonist treatment caused nonspecific changes that produced a weakened sensitized response. Importantly, DA antagonist treatment did not prevent the one-trial behavioral sensitization of preweanling rats. The latter result brings into question whether DA receptor stimulation is necessary for the induction of psychostimulant-induced behavioral sensitization during early ontogeny.

Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats

“…Importantly, the expression of behavioral sensitization on the test day is not dependent on whether psychostimulant-induced locomotor activity was present or absent on the pretreatment day. For example, an antagonist may leave locomotion unaffected on the pretreatment day, yet still attenuate sensitized responding on the test day [32,57]. Conversely, a full sensitized response may be evident on the test day despite psychostimulant-induced locomotor activity being reduced or prevented on the pretreatment day [29–32,57].…”

“…For example, an antagonist may leave locomotion unaffected on the pretreatment day, yet still attenuate sensitized responding on the test day [32,57]. Conversely, a full sensitized response may be evident on the test day despite psychostimulant-induced locomotor activity being reduced or prevented on the pretreatment day [29–32,57]. In perhaps the most extreme example, preweanling and adult rats anesthetized during the pretreatment phase (i.e., no locomotor activity was possible) exhibit behavioral sensitization on the test day [23,58].…”

Involvement of dopamine D3 receptor and dopamine transporter in methamphetamine‐induced behavioral sensitization in tree shrews

“…Behavioral sensitization refers to the enhancement of behavioral responses to repeated and intermittent drug exposure, including augmented autonomic activity and stereotypic behavior (Steketee & Kalivas, ). Drug‐induced behaviorally sensitized animal models are used routinely to define the cellular and molecular mechanisms underlying drug addiction and associated psychomotor behavioral alternations (Collins et al, ), and relevant tools have been developed to this effect (Kai, Nishizawa, Tsutsui, Ueda, & Kobayashi, ; Mohd‐Yusof et al, ). Further, pharmaceutical interventions can be introduced during the development of behavioral sensitization to evaluate the therapeutic effect on behavioral sensitization and reinstatement (Song et al, ; Sun et al, ; Zhao et al, ).…”

“…Further, pharmaceutical interventions can be introduced during the development of behavioral sensitization to evaluate the therapeutic effect on behavioral sensitization and reinstatement (Song et al, ; Sun et al, ; Zhao et al, ). The principal preclinical animal models of behavioral sensitization were rats (Mohd‐Yusof et al, ; Song et al, ; Zhao et al, ) and mice (Kai et al, ; Sun et al, ). Considering the significant differences in neuroanatomic structures and the functional divergence of the nervous systems of rodents and humans, however, these rodent‐based models may contribute limited understandings of addictive drugs' neurotoxicity and addictive behaviors in humans.…”

“…The mechanism of METH addiction has been studied intensively in the field of biomedicine. The neural circuits associated with METH addiction are very complex, involving multiple brain regions (Kai et al, ; Xu et al, ) and a multitude of neurotransmitters (Jiang et al, ; Jing, Liu, Zhang, & Liang, ) and protein mediators (Lee, Kim, Kim, Lee, & Jang, ; Mohd‐Yusof et al, ; Sun et al, ; Zhao et al, ). The incentive‐sensitization theory of addiction is one of the most widely accepted classical theories used to explain METH‐induced behavioral sensitization.…”