Effects of low‐dose scopolamine on locomotor activity: No dissociation between cognitive and non‐effects

Abstract

SUMMARYAttempts have been made to dissociate the cognitive effects of scopolamine from its noncognitive effects. It has been suggested that low doses of scopolamine may induce memory impairment without inducing significant non-cognitive effects. We therefore tested changes in locomotor activity (as a non-cognitive effect) in rats treated with low-dose scopolamine (which is believed to induce cognitive effects only).In this study, locomotor activity (as a non-cognitive effect) induced by low doses of this drug was evaluated by using two methods and rat strains. In the first study (circular box method, an automated open-field), scopolamine hydrobromide (HBr), scopolamine methylbromide (MeBr) or saline was injected subcutaneously into male Sprague-Dawley rats. After 30 min, rats were put into an automated open-field and locomotor activity was quantified by recording interruptions of infrared beams, with print-outs every 2 min for 16 min. Locomotor activity was assessed by summing these recordings. In the second study (closed platform), scopolamine HBr or saline was injected intraperitoneally into male Long-Evans rats. Twenty minutes later, the rats were placed in the center of a square-shaped closed platform (with 3x3 divisions). Locomotor activity was defined as the sum of crossings (traversing of four paws of the rat from one area into another of nine) and rears, which were recorded every 5 min for 20 min.Results from the circular box study showed that scopolamine HBr produced a marked increase in locomotor activity whereas scopolamine MeBr produced a non-significant decrease in locomotor activity. The closed platform data also demonstrated that scopolamine HBr increased locomotor activity significantly.These data show that scopolamine can induce non-cognitive effects (such as increased locomotor activity), even at low doses. Our results also imply that the increase in locomotor activity is mediated centrally.

The muscarinic system, cognition and schizophrenia

“…Jones et al, 2005;Thomsen et al, 2010;Ukai et al, 2004), an index of sensorimotor gating commonly used to model schizophrenia. Locomotor activity and stereotypy, two animal indicators of psychotic activity, have also been evoked using muscarinic antagonists (Chintoh et al, 2003;Gholamreza et al, 2002;Mathur et al, 1997), further highlighting the role the central muscarinic system may play in the symptomology of schizophrenia.…”

Differential effects of post-training scopolamine on spatial and non-spatial learning tasks in mice

“…However, Klinkenberg and Blokland (2010) emphasized that the reported effects of scopolamine on attention are ambiguous, due to differences in methodology (e.g., animal strains, experimental procedures, application method, targeted region). Moreover, given the 8-hour half-life of scopolamine (Malamed, 2018) and its posttraining administration, it seems unlikely that the results of this study can be reduced to attentionrelated processes, or for that matter, to previously reported non-cognitive effects (e.g., anxiety, locomotor activity) or peripheral side-effects (e.g., mydriasis, dry-mouth effect) of scopolamine (Gholamreza et al, 2002;Hodges et al, 2009;Jones and Higgins, 1995).…”

Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models

“…Mounting evidence suggests that scopolamine stimulates rodent locomotor activity, − likely acting via mesopontine cholinergic neurons that activate dopaminergic circuits controlling reward and locomotion . Mutant mice lacking the M5 receptor gene display increased scopolamine-induced hyperlocomotion, whereas atropine in combination with the α-adrenergic agonist clonidine produces pronounced hyperactivity in monoamine-depleted mice .…”