Evidence for multiple sites within rat ventral striatum mediating cocaine-conditioned place preference and locomotor activation

Abstract Considerable evidence suggests psychostimulants can exert rewarding and locomotor stimulating effects via increased dopamine transmission in the ventral striatum. However, the relative contributions of ventral striatal subregions to each of these effects have been little investigated. The present study examined the contribution of different ventral striatal sites to the rewarding and locomotor activating effects of cocaine. Initially, the effects of bilateral 6-hydroxydopamine lesions of the nucleus accumbens core or medial shell on cocaine-induced locomotor stimulation (0.5-1.5 mg/kg i.v. or 5-20 mg/kg i.p.) and conditioned place preference (0.5 mg/kg i.v. or 10 mg/kg i.p.) were examined. A subsequent study investigated the effects of olfactory tubercle vs. medial shell lesions on cocaine conditioned place preference and locomotor activity (0.5 mg/kg i.v.). Dopaminergic lesion extent was quantified by radioligand binding to the dopamine transporter. Multiple linear regression was used to identify associations between behavioral effects and residual dopamine innervation in ventral striatal subregions. On this basis, the accumbens core was associated with locomotor stimulant effects of i.v. and i.p. cocaine. In contrast, the medial shell was associated with the rewarding effect of i.v. cocaine, but not of i.p. cocaine. Finally, the olfactory tubercle was identified as an additional site contributing to conditioned place preference produced by i.v. cocaine. Overall, these findings provide additional evidence that the locomotor stimulant and rewarding effects of systemically-administered psychomotor stimulant drugs are segregated within the ventral striatum

Drug-Dependent Behaviors and Nicotinic Acetylcholine Receptor Expressions in Caenorhabditis elegans Following Chronic Nicotine Exposure

Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans’ (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-hour dosing) nicotine exposure at 6.17 and 61.7 μM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-hour 6.17 μM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7 μM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 “core” nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr-14, acr-16, acr-20, acr-21, ric-3, and unc-29) were significantly up-regulated following 61.7 μM nicotine treatment, in which worms showed significantly increased locomotion behavior. This study provides insights into the linkage between nicotine-induced locomotion behavior and the regulation of nicotinic acetylcholine receptors

Personalised learning in the open classroom: The mutuality of teacher and student agency

In this paper we examine how agency is characterised by teachers and students when personalised learning is enacted in the contemporary open classroom. A case study is outlined that identifies teacher reasoning for practice, the use of physical and virtual learning spaces, and student reaction to teacher facilitation of personalised learning. Agency is conceptualized as a multi-faceted set of behavioural, affective and cognitive choices, as realised by both teachers and students, drawing upon the action possibilities of contemporary educational contexts. A model of the mutuality of teacher and student agency is outlined. The model shows how a shared understanding of the affordances of flexible learning spaces and personalised learning interact to both produce teacher and student expectations and perceptions of their own and other’s choices and actions. Specific student choices and actions are examined in relation to problem-solving and open access of resources to achieve the task requirements. Implications are noted for teaching and learning in modern school contexts