Antidepressant activity opioids

Opioid peptides have also been tested in animal models of depression and of antidepressant activity. Enkephalins and endorphins decreased immobility in the forced swim test and in the learned helplessness paradigm, demonstrating... 

Experiments and data presented in this chapter demonstrate that delta opioid agonists have antidepressant-like effects in animal models used to measure antidepressant activity. The antidepressant-like effects can be separated from other behavioral effects produced by these compounds, such as locomotor stimulation, convulsions, and learning impairments. This separation lends validity to this potential target for depression by eliminating effects or sources that may produce false positives. These compounds should be tested in other models of antidepressant activity to confirm these findings in the forced swim test. 

To further develop delta opioid receptor agonists as potential therapeutics, more compounds should be developed and evaluated in the forced swim test and other models of antidepressant activity. This may allow for the identification of delta opioid agonists with even more selective behavioral effects. Indeed, there are a number of delta opioid agonists with different basic chemical structures that may prove useful. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

In addition to locomotor activity, delta opioid agonists produce convulsions in mice [41,43], rats [34,35], and monkeys [44 46], In the past, chemical-induced convulsions induced by camphor or pentylenetetrazol (Metrazol) were used as treatments for depression today, however, ECT is the only convulsant therapy used because the treatment-induced effects are less unpleasant than those produced by chemical convulsants [47]. ECS was demonstrated to have antidepressant-like effects in the forced swim test in rats [3], and ECT is a very effective treatment for depression in humans. Based on these observations, it was proposed that delta opioid agonists produce antidepressant-like effects tough a convulsive- or electroconvulsive shock (ECS)-like mechanism of action [41]. 

Although these experiments analyzed the hypothesis that convulsant activity is required for the antidepressant-like effects of ( + )BW373U86, it did not thoroughly address the question of whether seizure activity is required for the antidepressant-like effects of delta opioid agonists. The benzodiazepine midazolam was demonstrated to inhibit seizure activity [49,50] however, seizure activity was not directly measured in the study by Broom et al. [35]. Interestingly, limited work has been done with the seizure activity of delta opioid agonists. One study demonstrated that the delta opioid agonist... 

BW373U86 increased hippocampal type 2 theta power in rat EEG measurements however, this study did not test doses of BW373U86 that would produce convulsions in rats [51]. Therefore, it is difficult to determine the role of seizures in the antidepressant-like effects of delta opioid agonists. This concept must be studied in the future to determine the role of seizure activity or electroencephalographic activity in the antidepressant-like effects of delta opioid agonists. 

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