Available online at www.sciencedirect.com Neuroscience Letters 433 (2008) 235–240 Role of alpha1- and alpha2-adrenoceptors in the regulation of locomotion and spatial behavior in the active place avoidance task: A dose–response study Ales Stuchlik ∗ , Karel Vales Department of Neurophysiology of Memory and Computational Neuroscience, Institute of Physiology, Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic Received 28 November 2007; received in revised form 8 January 2008; accepted 10 January 2008 Abstract Studies on the neurotransmitter substrate of locomotion and place navigation occupy a central position in behavioral neuroscience. Active allothetic place avoidance (AAPA) is a task, in which animals are trained to avoid a room frame defined stable sector on a continuously rotating arena. The aim of the present study was to test the effect of the blockage of alpha1- and alpha2-adrenoceptors, using specific antagonists prazosin and idazoxan, on the locomotor activity and spatial behavior in the AAPA task. Both prazosin and idazoxan at the highest doses (4 and 6mg/kg, respectively) were found to decrease the locomotor activity in the AAPA and they also impaired navigational performance. The results suggest that antagonizing alpha-adrenoceptors with systemically administered drugs affects locomotor activity together with avoidance behavior and does not cause a purely cognitive deficit in the AAPA task. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Alpha1- and alpha2-adrenoceptors; Prazosin; Idazoxan; Avoidance; Learning; Locomotion; Memory Noradrenaline and adrenaline receptors are widely distributed throughout the central nervous system [1]. The majority of cen- tral noradrenergic projections originate in the brainstem nucleus locus coeruleus, from where neurons releasing noradrenaline, and to lesser extent adrenaline, project to various areas of the brain, including the neocortex, hippocampus, etc. The synap- tic effects of noradrenaline are mediated by two classes of receptors (alpha- and beta-), both coupled with G-proteins [17]. These classes are divided into subtypes, differing in ligand speci- ficity, kinetics, and effects. Alpha1- and beta-adrenoceptors were found to be mainly postsynaptic, whilst alpha2-adrenoceptors are localized both presynaptically and postsynaptically [1]. Alpha1 and alpha2 subtypes are expressed more widely in the central nervous system than beta-adrenoceptors [17], however, the beta-adrenoceptors exert important regulatory roles in vigi- lance and memory consolidation (e.g. [12]). The role of alpha- adrenoceptors is less known and usually not considered as cru- cial as that of beta-subtype. However, evidence from literature ∗ Corresponding author. Tel.: +420 241 062 538; fax: +420 241 062 488. E-mail address: stuchlik@biomed.cas.cz (A. Stuchlik). [3,6,8,22] suggests that alpha1- and alpha2-adrenoceptors may modulate locomotion, learning, and cognitive processes as well. When investigating neurotransmitter involvement in the behavior [10], a dry-arena spatial task, called active allothetic place avoidance (AAPA) [2], has proved to be a useful paradigm [18,19] allowing simultaneous assessments of locomotion and spatial efficiency [18]. In this task, animals are trained to move over a slowly rotating arena and avoid a sector, entering which is punished by a mild footshock [2]. The sector is defined in a stable position with respect to an experimental room. It was demonstrated that in place avoidance tasks, rats use both the intramaze cues (urine, droppings, and scent markings) as well as distal visual landmarks located in the room [23]. However, in the AAPA, both these classes of information are brought into a conflict by arena rotation. Therefore the animals must segregate spatial stimuli (both proximal and distal) into coherent representations of the arena and room [7] and to select the room frame as the only relevant for efficient performance in the task. This ability was described as hippocampal-dependent “cognitive coordination” in the important paper of Wesierska et al. [23]. Requirement of segregation of spatial information into classes [7,23] makes the task useful for studying animal 0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2008.01.013