Methamphetamine-induced stereotypy correlates negatively with patch-enhanced prodynorphin and arc mRNA expression in the rat caudate putamen: The role of mu opioid receptor activation

Abstract

Amphetamines induce stereotypy, which correlates with patch-enhanced c-Fos expression the patch compartment of caudate putamen (CPu). Methamphetamine (METH) treatment also induces patchenhanced expression of prodynorphin (PD), arc and zif/268 in the CPu. Whether patch-enhanced activation of any of these genes correlates with METH-induced stereotypy is unknown, and the factors that contribute to this pattern of expression are poorly understood. Activation of mu opioid receptors, which are expressed by the neurons of the patch compartment, may underlie METHinduced patch-enhanced gene expression and stereotypy. The current study examined whether striatal mu opioid receptor blockade altered METH-induced stereotypy and patch-enhanced gene expression, and if there was a correlation between the two responses. Animals were intrastriatally infused with the mu antagonist CTAP (10 μg/μl), treated with METH (7.5 mg/kg, s.c.), placed in activity chambers for 3h, and then sacrificed. CTAP pretreatment attenuated METH-induced increases in PD, arc and zif/268 mRNA expression and significantly reduced METH-induced stereotypy. Patch-enhanced PD and arc mRNA expression in the dorsolateral CPu correlated negatively with METH-induced stereotypy. These data indicate that mu opioid receptor activation contributes to METH-induced gene expression in the CPu and stereotypy, and that patch-enhanced PD and arc expression may be a homeostatic response to METH treatment.

Blockade of patch-based μ opioid receptors in the striatum attenuates methamphetamine-induced conditioned place preference and reduces activation of the patch compartment

“…Numerous studies have shown that enhanced activation of the patch compartment relative to the matrix compartment is observed during psychostimulant-induced stereotypy, and our studies have shown that an intact patch compartment is necessary for the expression of repetitive behaviors induced by psychostimulants (Adams et al, 2003; Canales and Graybiel, 2000; Graybiel et al, 1990; Horner et al, 2012; Horner and Keefe, 2006; Horner et al, 2010; Jedynak et al, 2012; Murray et al, 2014; Saka et al, 2004; Wang et al, 1995). The current study is the first that demonstrate that drug-mediated reward is also associated with enhanced activation of the patch compartment relative to the matrix compartment.…”

“…Our previous work indicated that blockade of striatal µ opioid receptors attenuated patch-enhanced activation and stereotypy following METH treatment (Horner et al, 2010). While it has been shown that central µ opioid receptors modulate psychostimulant-mediated reward (Schroeder et al, 2007), the specific contribution of patch-based µ opioid receptors is unknown.…”

Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration

“…At the end of the withdrawal period, COC-treated animals were given a challenge dose of COC (25 mg/kg, i.p. ), while SAL-treated animals were challenged with SAL and subsequently placed in plexiglass activity chambers (46 × 46 × 12 cm; (Frankel et al, 2007; Horner et al, 2012; Horner et al, 2010; Murray et al, 2014) for 2 hours, during which time behavior was recorded. Behavioral footage for each animal was analyzed post-hoc by a rater blind to experimental conditions.…”

“…Behavior was sampled for one minute every five minutes for the entire 2h observation period after injection of the challenge dose. Stereotypy was rated on a scale of 1–10, with 1 representing the minimal degree of response and 10 representing the maximal degree of response (Canales and Graybiel, 2000; Creese and Iverson, 1973; Horner et al, 2012; Horner et al, 2010; Murray et al, 2014). Stereotypy scores were obtained by averaging the scores from four other behavioral dimensions: repetitiveness/flexibility (the number of alternative motor responses emitted), frequency (the number of responses per unit time), duration (the percentage of time spent performing the most dominant response(s)), and the spatial distribution of the motor response which is an index of the confinement of the animal to a single location within the apparatus, with a higher score indicating a greater degree of confinement (Canales and Graybiel, 2000).…”

“…Stereotypy scores were obtained by averaging the scores from four other behavioral dimensions: repetitiveness/flexibility (the number of alternative motor responses emitted), frequency (the number of responses per unit time), duration (the percentage of time spent performing the most dominant response(s)), and the spatial distribution of the motor response which is an index of the confinement of the animal to a single location within the apparatus, with a higher score indicating a greater degree of confinement (Canales and Graybiel, 2000). Horizontal activity was defined as the number of quadrants the animal crossed on a 4 × 4 grid projected onto the recorded video using AnyMaze software (Stoelting, Wood Dale, IL, USA) and converted into centimeters (Frankel et al, 2007; Horner et al, 2012; Horner et al, 2010; Murray et al, 2014). …”