Abstract
Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 μg, 10 ng.kg–1 i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 μg, 10 ng) medication.
Introduction
One of the possible intriguing relationships may be the connection between ulcer disease and behaviour disturbances such as depression [10], [11]. As in depression, antidepressants are effective in relieving gastrointestinal lesions, both experimentally and clinically [5], [9], [12], [16], [31]. On the other hand, the opposite possibility that agents primarily designated as antiulcer drugs could vice versa be also effective in depression disorders has not been so far investigated. Based on its salutary effect on gastrointestinal lesions induced by various challengers [4], [13], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [33], [34], [35], [36], the novel stomach (antiulcer) pentadecapeptide, coded BPC 157 could be a valuable candidate. Besides, the possible role of such neuropeoptides as somatostatin, neuropeptide Y, and corticotropin, which are closely associated with the biogenic amines transmission, is already postulated in both conditions [8], [12]. Very recently, it was shown that BPC 157, which has no influence on gross behaviour of normal animals, blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice [6]. Thus, it seems likely that pentadecapeptide BPC 157 is also associated with the biogenic amines transmission [6]. In addition, the evidence that this pentadecapeptide would particularly interact with the catecholaminergic system, and particularly the central dopamine system, had been already noticed in this pentadecapeptide protection of gastric mucosa during stress [27]. A significant pool of BPC has been immunohistochemically shown in the stomach and also in the brain [21].
Therefore, the focus was on the mentioned pentadecapeptide, BPC 157, given in its known antiulcer regimen [21], [23], [25], [26], [27], [28], [29], [30], and its efficacy on animal depression was evaluated in different experimental models [37], [38], [39] in comparison with conventional agents. Finally, considering the likely significance of the serotonin system for depression disorders, and the not fully elucidated importance of most serotonin in gastrointestinal tract (i.e., 90% of total serotonin) [32], the possibility that the stomach pentadecapeptide BPC 157 could have a beneficial influence in depression models may not be entirely unexpected.
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Section snippets
BPC 157. Preparation of the peptide
The pentadecapeptide BPC 157 (Gly Glu Pro Pro Pro Gly Lys Pro Ala Asp Asp Ala Gly Leu Val), M.W. 1 419 freely soluble in water at pH 7.0 and in saline, was prepared as described in detail previously [4], [6], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]. A peptide with 99% (HPLC) purity (1-des-Gly peptide as impurity) was used.
Animals
Female, Albino rats of Fisher-344 strain, 180–200 g b.w. were used in all of the experiments. They were housed in single cages 5 d before the
Porsolt's procedure
The applied procedure produced a significant period of immobility in all of the control saline rats (table I). Imipramine and nialamide, given in their usual regimen, used as reference agents, significantly reduced the otherwise consistently raised immobility time in rats subjected to Porsolt's procedure, along with the previously described data (i.e., [38]). An essentially similar effect was noted with pentadecapeptide BPC 157 application (i.e., BPC 157 10 μg and 10 ng.kg–1 b.w. vs. imipramine
Discussion
In these experiments, pentadecapeptide BPC 157, primarily designated as an antiulcer agent with cyto/organoprotective activity [21], [23], [25], [26], [27], [28], [29], [30], was shown to reduce the duration of immobility in a way that might be typical of the re-uptake (serotonin, noradrenaline) of inhibitor antidepressants [38]. Of note, a positive effect was consistently observed in both of the tested models. In general, these findings were obtained in these two distinctive models, using the
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