Evaluation of Dynorphin A(1-13) and E-2078, a Dynorphin Analogue, and their Effects in Morphine-Treated Rhesus Monkeys Using Directly Observable Signs, Drug Discrimination, Rates of Responding, Antinociception and Respiration

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Authors
Injety, Kalpana Rejina
Issue Date
1995
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Thesis
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en_US
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Abstract
At present, there are varied forms of treatment for opioid addiction and dependence, yet, there is much room for improvement. These issues call for new and varied treatment plans. The endogenous opioid peptide, Dynorphin A(1-13) (DYN) and its metabolically stable analogue E-2078, have been shown to have interesting properties in Morphine-(MS)-dependent subjects. DYN has been shown to attenuate MS withdrawal signs in a few different species and has also been shown to potentiate the antinociceptive effects of MS in rodents. There has been relatively little research done with E-2078, however, it has been shown to produce antinociception in both MS-dependent and non-dependent subjects. These findings suggest that DYN and E- 2078 could be used both as treatments for opioid addiction and as therapeutic agents for pain relief. To characterize and compare some effects· of DYN and E-2078, experiments utilizing both drugs along with a variety of other opioid and non-opioid drugs were performed. Experiments were performed in four MS-treated, female, rhesus monkeys. Subjects were assessed for directly observable signs, drug discrimination responses, rates of responding, antinociception and respiration. For data analysis of antinociception and respiration, results from untreated subjects were compared with those of MS-treated subjects. Results obtained indicated that DYN and E-2078 have similar behavioral effects. In the subjects studied, MS withdrawal was not attenuated and antinociception was only produced in untreated subjects. Respiration studies established controls for further experimentation and evaluated MS tolerance.
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iv, 54 p.
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