Brain Research 888 (2001) 311–313
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Short communication
Diazepam and nicotine increase social interaction in gerbils: a test for
anxiolytic action
*
Sandra E. File , Survjit Cheeta, Chioma Akanezi
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King’s College London, Guy’s Campus,
London SE1 1UL, UK
Accepted 10 October 2000
Abstract
The effects of two drugs with anxiolytic actions, diazepam (0.1, 0.3 and 1 mg / kg) and nicotine (0.1 and 0.5 mg / kg) were examined on the time spent in social interaction by pairs of male gerbils. In a test arena lit by high light, diazepam (0.1 mg / kg) increased social interaction, without changing locomotor activity. Diazepam (0.3 and 1 mg / kg) produced a dose-related increase in locomotor activity, which reached significance at the higher dose. Nicotine produced a dose-related increase in social interaction, which reached significance at 0.5 mg / kg, but was without effect on locomotor activity. The specific increases in social interaction observed with diazepam and nicotine are similar to those seen in the well-validated social interaction test of anxiety in rats and suggest that social interaction in gerbils may also be used to screen for anxiolytic action of novel compounds. 2001 Elsevier Science B.V. All rights reserved.
Theme: Disorders of the nervous system
Topic: Neuropsychiatric disorders
Keywords: Anxiety; Benzodiazepines; Nicotine
The social interaction test in rats is one of the most were housed in groups in a dimly lit room (3 lux; light on extensively validated animal models of anxiety [10,11]. 08:00 to 20:00 h) with food and water freely available. The When social interaction is suppressed by testing under high gerbils were left undisturbed for one week before testing. light, anxiolytic effects of diazepam, nicotine and the This study was in compliance with the UK Home Office substance P receptor antagonists CGP 49823 and NKP608 Regulations.
have been detected and are shown by increases in the time The test arena was a wooden box 40340 cm with 27 cm
spent in social interaction, without changes in locomotor walls and a solid floor, lit by bright light (1400 lux). A activity [5–7,9,12,13,15,20,21]. Phylogenetic differences video camera was mounted directly over the test arena and in the substance P receptor, for which the pharmacology of the gerbils were observed from a screen in an adjacent the human receptor resembles that in gerbils, rather than area. An observer, blind to the drug treatment of the that in rats or mice [18,19] have highlighted the need for animals, scored the time spent in active social interaction. animal tests of anxiety in other species. The present Locomotor activity was assessed from videotapes, by experiment sought to determine whether a social inter- placing a squared grid over the screen and counting the action test in gerbils could be used to detect anxiolytic number of squares crossed.
activity of diazepam and nicotine. Diazepam (Roche Products, Welwyn Garden City, UK) Male adult Mongolian gerbils (Central Biomedical was suspended with a drop of Tween-20 in 20 ml of Services, University of Leeds, UK), approximately 60 g, distilled water and left in an ultrasonic water bath for 20 min before injection. (2)-Nicotine hydrogen tartrate
(Sigma, Poole, UK) was dissolved in distilled water to various concentrations so that the volume of injection was
*Corresponding author. Tel.:144-20-7848-6667; fax: 1
44-20-7848-constant at 2 ml / kg. The control groups received equal
6660.
E-mail address: sandra.file@kcl.ac.uk (S.E. File). volume injections of the appropriate vehicle. All injections
312 S.E. File et al. / Brain Research 888 (2001) 311 –313
[F(3,44)55.6, P,0.0025] and Fisher’s tests showed that
the 0.1 mg / kg dose was significantly different from the controls (Fig. 1). Diazepam also increased locomotor activity [F(3,41)54.3, P,0.01], but only the 1 mg / kg
dose differed significantly (P,0.01) from the controls,
Table 1.
Nicotine significantly increased social interaction in a dose-dependent manner [F(2,22)53.6, P,0.05], but on
post-hoc tests only the 0.5 mg / kg dose reached signifi-cance, Fig. 1. Nicotine was without effect on locomotor activity [F(2,22)50.3, Table 1].
The results of this study show that diazepam increases social interaction in gerbils, at a dose that does not change locomotor activity. This pattern of results indicates an anxiolytic action and is similar to that previously estab-lished in the rat social interaction test of anxiety [5–7,9]. In the rat social interaction test, anxiolytic effects, shown
Fig. 1. Mean6S.E.M. time (s) spent by pairs of gerbils in social
by increases in social interaction, have been reported from
interaction after i.p. injection of vehicle (Veh), diazepam (0.1 mg / kg;
0.125 mg / kg diazepam [5–7], with decreases in locomotor
Diaz) or (2)-nicotine (0.5 mg / kg; Nic). *P,0.05 compared with
activity occurring from 1 mg / kg. The gerbil is at least as
respective vehicle control group.
sensitive as the rat to the anxiolytic effect of diazepam, but differs from the rat in that the limiting effects of higher were intraperitoneal (i.p.) 30 min before testing and both doses are due to locomotor stimulation. This effect could members of a test pair received the same drug treatment. limit the increase in time spent in social interaction due to Pairs of gerbils were randomly allocated among the response competition. The increased locomotor activity following groups: observed in the gerbil after diazepam resembles the effects Experiment 1: vehicle (n518); diazepam 0.1 mg / kg of benzodiazepines in the mouse, rather than the rat
(n511), 0.3 mg / kg (n58), 1 mg / kg (n58). [1,8,14,17]. However, there was a 10-fold separation in the
Experiment 2: vehicle (n57); nicotine 0.1 mg / kg (n5 dose that increased social interaction and the dose that
11), 0.5 mg / kg (n57). increased locomotor activity, suggesting that the gerbil
The day before social interaction testing, each gerbil was social interaction test could be a useful screen for com-placed singly into the test arena and given a 10-min pounds acting at the benzodiazepine receptor.
familiarisation trial. Pairs of gerbils were placed into the A dose-related increase in social interaction was also centre of the test arena and their social interaction (snif- seen in the gerbils after nicotine and neither dose caused fing, following, grooming the partner, wrestling) scored for any change in locomotor activity. In the rat, 0.1 mg / kg 4.5 min. After each trial, any boluses were removed and nicotine increased social interaction, without change in the floor was wiped with damp paper towel. They were locomotor activity, but at 0.5 mg / kg both social interaction tested in an order randomised for drug treatment, between and locomotor activity were decreased [15]. The gerbil 10:00 and 13:00 h. social interaction test is sensitive to the anxiolytic effect of The data were analysed with one way analyses of nicotine at doses similar to those that are effective in the variance, followed by Fisher’s tests to establish the signifi- mouse black–white crossing test [4] and the mouse cance of individual doses. elevated plus-maze [2,3,16].
Diazepam significantly increased social interaction In conclusion, the social interaction test in gerbils would
Table 1
Mean (6S.E.M.) time (s) spent in social interaction and locomotor activity (squares crossed) by pairs of gerbils treated in experiment 1 with vehicle or diazepam (DZ 0.1, 0.3 or 1 mg / kg) and in experiment 2 with vehicle or nicotine (NIC 0.1 or 0.5 mg / kg)
Experiment 1 Vehicle DZ 0.1 mg / kg DZ 0.3 mg / kg DZ 1 mg / kg
Social interaction 33.864.7 53.866.9* 40.5610.2 15.663.2
Locomotor activity 92.166.7 89.4610.8 112.067.9 136.7616.6**
Experiment 2 NIC 0.1 mg / kg NIC 0.5 mg / kg
Social interaction 27.964.6 36.664.3 51.369.5*
Locomotor activity 81.169.8 78.667.4 86.966.0
S.E. File et al. / Brain Research 888 (2001) 311 –313 313
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