Comparison of Desipramine, Amitriptyline, Zimeldine and Alaproclate in Six Animal Models Used to Investigate Antidepressant Drugs

Abstract

In the present paper the acute actions primarily of the tricyclic antidepressants amitriptyline and desipramine, the atypical antidepressant zimeldine and the potential antidepressant alaproclate were evaluated in six models used for studying antidepressant agents. These included the forced swim test, a modified learned helplessness procedure, the clonidine hypothermia test, the social dominance test (using the interaction with clonidine), a differential-reinforcement-of-low-rates (DRL-72s) schedule and conditioned avoidance response. The results showed desipramine to be effective in all the tests employed. Zimeldine was effective in the learned helplessness, DRL-72s and domination tests, but also caused notable deficits in two-way active avoidance response. Alaproclate was effective in all the tests except the domination paradigm. Amitriptyline was effective in all tests employed. The results are discussed in relation to the possible mechanism of action of these compounds in the test models employed.

Neither the 5-HT1A- nor the 5-HT2-Receptor Subtype Mediates the Effect of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Forced-Swimming-Induced Immobility in Mice

“…These results are consistent with findings that serotonergic drugs are clinically active in the treatment of depression (1). It has been suggested that SSRIs are not effective in the forced-swimming test (8), and another report indicated that norepinephrine reuptake inhibitors, but not SSRIs are effective in this model (9). However, we found the significant effect of fluvoxamine in this model.…”

Antidepressant-like effects of pregnancy and progesterone in Wistar rats as measured in the differential reinforcement of the low-rate 72 s task

“…The DRL-72 s task is designed to test the antidepressant profile of drugs (Danysz et al 1988). In this task, rats are required to press a lever to obtain water or food, but they must withhold their response for 72 s to obtain a reinforcer.…”

Differential modulation of efficiency in a food-rewarded "differential reinforcement of low-rate" 72-s schedule in rats by norepinephrine and serotonin reuptake inhibitors

“…Further, the "atypical" agents mirtazapine and mianserin, which possess 5-HT 2C and α 2 -adrenoceptor (AR) antagonist properties, similarly improve DRL 72-s performance by increasing reinforcement rates and/or decreasing response rates (O'Donnell and Seiden 1983;Marek et al 1989b;Hand et al 1991;Jackson et al 1995;Jones et al 1998). Tricyclic agents, such as clomipramine, amitriptyline and imipramine, are also effective as shown by a decrease in response rates, which may or may not be accompanied by an increase in reinforcement rates Seiden 1980a, 1980b;O'Donnell and Seiden 1983;Howard and Pollard 1984;Danysz et al 1988;Van Hest et al 1992;Olivier et al 1993;Borsini et al 1997).…”

“…Indicative of the significance of serotonergic mechanisms in the actions of antidepressant in the DRL 72-s procedure, 5-HT reuptake inhibitors (SSRIs) have been shown to be effective as judged by an increase in reinforcement rates and/or a decrease in response rates (Seiden et al 1985;Danysz et al 1988;Marek et al 1989a;Olivier et al 1993;Richards et al 1993;Bright et al 1997;Jones et al 1998;Wong et al 2000), as well as by "peak deviation analysis of IRT distribution" (Sokolowski and Seiden 1999). In support of a role of serotonergic pathways, serotonin (5-HT) 1A agonists display an antidepressant-like profile in the DRL 72-s procedure, while depletion of central pools of 5-HT interferes with performance in the DRL 72-s protocol and in models of delayed reinforcement (Fletcher 1995;Ho et al 1998;Bizot et al 1999;Jolly et al 1999).…”