Effects of imipramine on anxiety and depressive-like behavior and body weight gain in rats housed in overcrowded conditions

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Abstract

Long-term crowding in rats can lead to anxiety-depressive disorders. Antidepressants, including Imipramine, are used in clinical and experimental settings to correct such states. The aim of this study was to test whether Imipramine has an antidepressant and/or anxiolytic effect on the behavior of rats kept in overcrowded conditions. We studied the effect of daily (4 days before and 10 days during crowding) intraperitoneal injections of Imipramine at a dose of 10 mg/kg on the behavior in tests for anxiety (open field, light-dark, and elevated plus maze – EPM) and in forced swimming test after Imipramine withdrawal (12–15 days of overcrowding) in rats housed in overcrowded (16 rats per cage) and standard (4–5 rats per cage) conditions. Also, body weight gain on days 8 and 12 of overcrowding and the blood plasma corticosterone level on day 16 of overcrowding were assessed in the same groups of rats. Overcrowding led to activation of behavioral reactions in the light-dark and EPM tests, which did not decrease (with the exception of three indicators) after Imipramine treatment. So, Imipramine did not have a significant corrective effect in these tests on the behavior of rats kept in overcrowded conditions. In the forced swimming test under overcrowded conditions, an increase in immobility was observed, and imipramine led to the correction of this disorder. Body weight gain decreased after treatment of Imipramine in standard and overcrowded (to a greater degree) conditions, which may indicate a negative side effect of the antidepressant. The level of corticosterone in blood plasma did not differ in rats kept in overcrowded and standard conditions and did not change under the influence of Imipramine. Thus, the antidepressant Imipramine had a therapeutic effect on increased immobility in the forced swim test in rats under overcrowded conditions. This suggests that the behavioral changes observed in this test in rats under crowded conditions are depressive-like behavioral disorders. That is, imipramine had a pronounced antidepressant effect in the forced swimming test.

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About the authors

E. V. Loseva

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Author for correspondence.
Email: losvnd@mail.ru
Russian Federation, Moscow

N. A. Loginova

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

A. A. Potekhina

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

N. D. Broshevitskaya

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

O. V. Kurskaya

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

M. I. Zaichenko

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

K. Y. Sarkisova

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

Email: losvnd@mail.ru
Russian Federation, Moscow

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2. Fig. 1. Body weight gain (g) in groups of rats kept under standard conditions (St) or overcrowded conditions (Oc), after daily i.p. administration of saline solution (SS) or imipramine (IM) at a dose of 10 mg/kg. Groups of rats kept under St conditions: St+SS – control after SS administration; St+IM – after IM administration. Groups of rats kept under Oc conditions: Oc+SS – control after SS administration; Oc+IM – after IM administration. The ordinate axis shows body weight gain values ​​in all groups 8 and 12 days after crowding of rats from the Oc+SS and Oc+IM groups. Data are presented as mean ± SEM: *tp < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001 compared to the group indicated by the short vertical line at the end of the horizontal line (group comparison according to the Newman–Keuls test). In addition, individual values ​​of body weight gain for each rat are given (circles to the right of the bars indicating the corresponding groups).

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3. Fig. 2. Behavioral indices in the light-dark test in groups of rats kept under standard conditions (St) or overcrowded conditions (Oc), three days after the cessation of daily (14 days) i.p. administration of saline (S) or imipramine (IM) at a dose of 10 mg/kg. Groups of rats kept under St conditions: St+S – control after administration of SS, white column; St+IM – after administration of IM, light gray column). Groups of rats kept under Oc conditions: Oc+S – control after administration of SS, dark gray column; Oc+IM – after administration of IM, black column. (a) – Light box, total duration of visits, s. (b) – Light box, average duration of visit, s. (c) – Peeping out, number of acts. (d) – Pilling out, number of acts. (e) – Rears, total duration, s. (f) – Rear, average duration, s. (g) – Sniffing, total duration, s. (h) – Sniffing, average duration of act, s. Data are presented as mean ± SEM: *ttp < 0.2, *tp < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001 compared to the group indicated by the short vertical line at the end of the horizontal line (group comparison according to the Newman–Keuls test). In addition, individual values ​​for each rat are given (circles to the right of the columns indicating the corresponding groups).

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4. Fig. 3. Behavioural indices in the elevated plus maze (EPM) test in groups of rats kept under standard conditions (St) or overcrowded conditions (Oc), four days after the cessation of daily (14 days) i.p. administration of saline (S) or imipramine (IM) at a dose of 10 mg/kg. Groups of rats kept under St conditions: St+S – control after administration of SS, white column; St+IM – after administration of IM, light grey column). Groups of rats kept under Oc conditions: Oc+S – control after administration of SS, dark grey column; Oc+IM – after administration of IM, black column. (a) – center, total duration of visits, s. (b) – Enclosed arms, number of visits, s. (c) – Sniffing, number of acts. (d) – Sniffing, total duration, s. (e) – Rears, number. (f) – Rear, average duration, s. (g) – Handing, total duration, s. (h) – Peeping out, number of acts. Data are presented as mean ± SEM: *ttp < 0.2, *tp < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001 compared to the group indicated by the short vertical line at the end of the horizontal line (group comparison according to the Newman–Keuls test). In addition, individual values ​​for each rat are given (circles to the right of the columns indicating the corresponding groups).

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5. Fig. 4. Behavioral indices in the forced swimming test in groups of rats kept under standard conditions (St) or overcrowded conditions (Oc), four days after the cessation of daily (14 days) i.p. administration of saline (S) or imipramine (IM) at a dose of 10 mg/kg. Groups of rats kept under St conditions: St+S – control after administration of SS, white column; St+IM – after administration of IM, light gray column. Groups of rats kept under Oc conditions: Oc+S – control after administration of SS, dark gray column; Oc+IM – after administration of IM, black column. (a) – duration of the first episode of active swimming, s. (b) – Latensity of the first episode of immobility, s. (c) – Total immobility time, s. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01 compared to the group indicated by the short vertical bar at the end of the horizontal line (group comparison according to the Newman–Keuls test). In addition, individual values ​​of the parameters for each rat are given (circles to the right of the columns indicating the corresponding groups).

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