1The University of veterinary medicine, Košice, The Slovak Republic, [email protected] ; 2The Psychiatric
Hospital, 65 Dr. Zelenyáka St., 935 61 Hronovce, The Slovak Republic ; 3The Pharmaceutical Faculty of the
UVP, Brno, The Czech Republic
ABSTRACT
In 20 rabbits (two groups, 10 control and 10 experimental animals, Ø = 3,1; σn = 0,54 kg b.w.) has been studied the interaction effect of morphine hydrochloride (5.0 mg.kg b.w.) with the rabbits tissues. We administered to experimental rabbits the active substance using preparation Morphin Biotika 1% inj. intramuscularly and we observed the animals’ responses on the i.m. administration and the responses were compared with the control animals. In our experiments morphine induced very significant calming and depressive effect on the behaviour of rabbits in contrast to control animals. Except of described, morphine induced similarly very significant inhibition of respiration rate (P<0.0005) and also reduced body temperature (P<0.0005). The effect of morphine on the heart rate was milder. All these data have been compared with the rabbits of control group to be sure about the effect of morphine during the interaction studies.
INTRODUCTION
Morphine as a model opioid agent is in the central interest of studies for many scientific teams, especially in connection with its intensive analgesic activities in various types and breeds of animals (Gagliese and Katz 3, Prado 6, Rajagopal et al. 5). Morphine and some other opioids belong to the strong analgesics and so they are able to suppress very effectively pain at the various states & situations (Bell et al. 1, Cepeda et al. 2, Mercadante et al. 4). The aim of these experiments was the study of interaction effect of morphine with the rabbit’s tissues and comparison the behavioural reaction of experimental animals with the controls.
MATERIAL AND METHODS
We used two groups of rabbits (10 control and 10 experimental animals, Ø = 3,1; σn = 0,54 kg b.w.) We administered to each experimental rabbit 5.0 mg.kg-1 b. w. of morphine hydrochloride (Morphin Biotika 1%
inj.) and other group was control. We observed the clinical behaviour of rabbits of both groups as well as following selected parameters: respiration-rate, heart-rate, and also the body temperature at the various time periods. The first measurement was at -0.5 h before experiments and then also at 0.5; 1; 3; 6 and 24 h after the administration of drugs to rabbits. For measurement we used Hartmann digital Maximum thermometer and other measures in accordance with lege artis. The results obtained were evaluated statistically using PC Intel Celeron with programme Microsoft 98 Excel with t-test using the appropriate comparisons between experimental and control groups in various schemas of comparisons.
RESULTS AND DISCUSSION
We observed an induction of very significant calming and sedation effects on the behaviour of rabbits and their retreat to the back parts of the cage with their heads resting on the floor after i. m. administration of morphine into experimental rabbits (since 30 min. of the experiment to 6 h). In great majority of these experimental rabbits was observed miotic state of pupil since 11 min. of experiment and lasted for more than one and half hour. We must present however the fact that this calming and sedation effect has not been observed in the parallel control animals. The rabbits of control animals were in contrast to experimental animals very brisk, with the keeping head straight and without presence of observable abnormalities. If we take into account also the results of measured parameters of both animal groups they were also very interesting. In our experimental rabbits we have registered that after the administration of morphine there
were present very significant suppressions of respiration-rate, which were evident at the comparison with the state of the same animals before administration of morphine. But evidently were also significant when we took into an account the animals of control group. Both comparisons of data with the data before starting of experiments and also with parallel measured values of other group at the passing time measurements were very significant (P<0.0005). Similarly as with the changes of respiration, we have registered also interesting changes in the values of body temperature. Observed results demonstrated, that intramuscularly administered morphine hydrochloride induced in experimental rabbits decreases the body temperature. These were registered again both in comparison with the data before starting of experiments in the same group of animals, as well as with the both data of control animals i.e. with the data before starting of experiments, and also with parallel passing temporal time measurements. The differences of observed criterion were very significant among the studied groups of animals (P<0.0005). Used opiate analgesic has also influence on the functional activity of heart musculature. However, we must say that morphine hydrochloride influenced the extend of heart-rate in the lower level (P<0.01), as it was in cases of above described two other important criteria. Morphine is still experimentally studied in many animals (Gagliese and Katz 3, Prado 6, Rajagopal et al. 5), with the aim for suppression of pain in various patients (Bell et al. 2003, Cepeda et al. 2, Mercadante et al. 4). That is why the knowledge on the opioid interactions with the animal tissues is useful. Literature indicates that opioids may interact with various receptors and some examples of them can be seen in inserted table bellow.
Table. 1. An overview of the proposed functions of some receptors participating in regulation of certain activities in the animal body - literature compilate
Receptors
µ-1 µ-2 κ δ
Supraspinal and spinal analgesia
Analgesia Supraspinal and spinal
analgesia
Supraspinal and spinal analgesia
Depression of respiration Sedation Depression of respiration
(Euphoria in humans) Dysphoria ?
Miosis Miosis ?
Strong constipation Obstipation
Bradycardia ? ? ?
Hypovolemia ? ? ?
Retention of urine Diuresis Retention of urine
REFERENCES
1. Bell, R.F.: J. Pain Sympt. Manag., 2003, 26, 3, 867-875. 2. Cepeda, M.S. et al.: Clin. Pharm. Therap., 74,2,2003,102-112. 3. Gagliese, L., Katz, J.: Pain, 103,1-2, 2003, 11-20.
4. Mercadante, S. et al.: J. Pain Sympt. Manag., 26, 2, 2003,769-775.
5. Rajagopal, A., Kala, S., Bruera E.: J. Pain Sympt. Manag., 2003, 26, 3, 786-788. 6. Prado WA: J. Neurosci. Methods, 129, 1, 2003, 33-39.