- Email: [email protected]
Participation of opioid mechanism on the antinociceptive effect induced by (+)- and (−)- oxaprotiline in two behavioural pain tests in mice
B. Preclinical [2] Takagi, H., H. Shiomi and H. Amano, (1979) A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser. Natore 282; 410-412; 1979
ElB-35
Effect of tramadol analgesia
and
clonidine
on stress-induced
I. Panocka, B. Antkowiak, M. Kowalczyk. Department Military
Institute
of Hygiene
and Epidemiology,
of Pharmacology, Warsaw, Poland
Tramadol is a centrally acting, synthetic analgesic with opioid agonist properties. Experimental data suggest that tramadol may exert part of its analgesic effect through the activation of central inhibitory rnonoaminergic pathways. Systemically administered antagonists of noradrenergic and serotonergic receptors block the antinociception of spinally administered tramadol, but not morphine in the rat tail-flick test. Clonidine is a selective alpha2 adrenergic agonist which shows marked analgesic activity after spinal administration. In our experiments, we studied analgesic properties of tramadol together with systemically administered clonidine before and after stress using tail-immersion test. The experiments were performed on adult male Wistar rats weighing 250-350 g with reversed light/dark cycle. The tail-withdrawal latency following immersion in hot water (55’ C) was measured before and 2, 30 and 60 minutes afier stress (3 min. swimming in water at 20” C). Rats received intraperitoneal injections of tramadol (20 mgkg) or clonidine (50 Kg/kg) or tramadol co-injected with clonidine at the same doses 30 min. before stress. The control group received aqua pro iniectione. The results were expressed as percentage of maximal possible effect (% MPE) according to the formula: (postdrug latency - baseline latency)/(cut-off time - baseline latency) x 100%. Statistically significant differences between the groups analysed were determined using t-test. Before the swimming stress,both tramadol and clonidine given separately and injected together revealed a statistically significant analgesic effect in comparison with the control group. The analgesic effect of tramadol co-injected with clonidine was significantly greater than in the case of the drugs given separately. After stress tramadol together with clonidine produced a significant analgesic effect at minute 2 and 30, tramadol given separately - only at min. 2 and clonidine had no significant effect. Just after the stress,there was no difference between the efficacy of tramadol alone and tramadol together with clonidine. In our experiment the activation of alphal-adrenergic receptors potentiated the analgesic effect of tramadol before and 30 min. after but not just after stress. References [l]
Raffa, R.B. et al., 1992. Opioid and non-opioid mechanisms of action of tramadol, an ‘atypical’ analgesic. J. Pharmacol. Exp. Ther. 260, 275-85. [2] Desmeules, J.A., Pigwt, V., Collart, L., Dayer, P, 1996. Contributin of monoaminergic modulation to the analgesic effect of tramadol. Br. J. Clin. Pharmacol. 41, 7-12.
18-361
Involvement antinociceptlve
of histamlnergic system effect of Tyr-MIF-1
in the
A. Bocheva’, R. Zamfirova’ , W. Scbunack’, S. Todorov’ *. ‘Institute
of Physiology Bulgarian Academy of Science, 23 Acad. G. Bonchev St., I I I3 Sofia. Bulgaria ‘Institut ftir Pharmazie, Freie Universitiit, Kiinigin-Luise-Spaye 2 + 4, I4195 Berlin, Germany
Tyr-MIF-1 is a representative of the MlF’s family of endogenous peptides. It has been isolated from bovine hypothalamus and human parietal cortex that suggests its involvement in nociception. Tyr-MIF- 1 can bind to the p-receptors as well as to its specific non-opiate receptors in the brain. Data in the literature rise the idea that histamine (HA), a well known nociceptive agent, and ‘I@MIF-1 might have a common pathway in their effects on nociception. We tested that possibility by investigating the combined action of FUB 94 (a precursor of the H3-agonist R-amethyl histamine) and Tyr-MIF-1 on nociception. The changes in the
s33
Studies
nociceptive effects were examined in male Wistar rats by the RandallSellito paw-pressure (PP) test, using an analgesimeter (Ugo Basile). A pressure was applied to the hind paw and its magnitude (in g) required to elicit nociceptive responses (squeak and struggle) was taken as the mechanical nociceptive threshold. A cut-off value of 500 g was used to prevent damage of the paw. Tyr-MiF-1 in a dose of 1 mg/kg exerted a strong naloxone-reversible analgesic effect. FUB 94 (5 mg/kg, i.p.) had an antinociceptive action, too. The co-administration of Tyr-MIF1 and FUB 94 increased the antinociceptive effect of the H3-agonist precursor. This effect was reversed when methylene blue (MB, 500 pg/rat) was applied 1 hour before the combination. The results obtained confhmed the hypothesis that second messengers might be involved in the realization of the nociceptive effects of both HA and Tyr-MIF- 1. This study was supported by Grant B-601 of the NSF, Bulgaria. 16-371
Participation antinocicedive oxaprotilik mice
of opioid mechanism on the effect induced bv (+I- and I-)in two behavioural pain’ tests in-
A. WesoIowska, J. Borycz. Institute of Sciences,
12 Sm@na Street, Krakow,
of Pharmacology, Poland
Polish
Academy
Oxaprotiline (OXA), a hydroxy derivative of maprotiline, has two optic isomers which exert an antidepressant action in patients (Delini-Stola et al., 1988). (+)-OXA is a highly selective noradrenaline uptake inhibitor, while (-)-OXA is devoid of such an activity (Waldmeier et al., 1982). The mechanism of clinical action of (-)-OXA has not been elucidated, as yet. Irrespective of its antidepressant activity, (+)-Ox4 produces antinociceptive effects in mice (Gray et al., 1998), however no studies of this type have been conducted for (-)-OXA. The purpose of the present study was to assess the activity of both OXA enantiomers in two experimental models of pain in mice, a hot plate (HPL) test and a writhing syndrome (WS) induced by phenylbenzoquinone, and to determine whether the opioidergic system may be engaged in their antinociceptive effects. Both OXAs were administered intraperitoneally to mice 1 h before the test. Administration of (+)-OXA (0.31-20 m&g) and (-)-OXA (20 m&g) produced a statistically significant elevation of the nociceptive threshold, measured by the increased latencies in the HPL test. Moreover, (+)-OXA (0.62-20 mg/kg) and (-)-enantiomer (5-20 m&g) decreased the number of writhing episodes induced by phenylbenzoquinone in mice. The analgesic effect induced by (+)-OXA (0.31 mg/kg) in the HPL test in mice was abolished by naloxone (2 mgkg, subcutaneously), an opioid antagonist. In the WR test, naloxone (2 m&g) partially, but not significantly, reduced the antinociceptive responses induced by (+)-OXA (0.62 m&g). The antinociceptive action of (-)-OXA (20 mgikg in the HPL test, or 5 mgikg in the WS test) was practically blocked by naloxone
(2 NW.
Naloxone given alone (2 m&g) 10 min before the test did not affect the nociceptive responses in comparison with the effect observed in animals receiving saline in both the tests used. The obtained results show that both OXA enantiomers produce antinociception in the HPL and the WR tests in mice, (+)-enantiomer (a noradrenaline uptake inhibitor) being more effective than (-)-OXA in either test. The endogenous opioid system seems to be implicated, at least partially, in their antinociceptive action. Possible participation of other neurotransmitter systems in the antinociceptive responses induced by both OXA enantiomers will be fhe aim of our further studies. References [l]
Delini-Stala, A., Vassout, A., Hanser, K., Bittiger, H., Buch, O., Olpe, H.R. (1988) Oxaprotiline and its enantiomcrs: do they open new avenues in the research on the mode of action of antidepressants? In: Usdin, E., Goldstein, M., Friedhoff, A., Georgotal, A. (eds.) Frontiers in Neuropsychiatric Research, Macmillan, London, pp. 121-134. [2] Gray, A.M., Spencer, W.J., Sewll, R.D.E. (1998) The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds. Br. J. Pharmacol. 124,669-674.
s34
B. Preclinical
[3] Waldmeier,
P., Bauman, P., Hauser, H., Maitre, L., Storni, A. (1982) Oxaprotiline, a noradrenaline uptake inhibitor with an active and inactive enantiomer. B&hem. Pharmacol. 31, 2169-2176
m
Involvement nociceptive
of adrenergic neurotransmission activity of Tyr-MIF-1
A. Bocheva, R. Zamlirova’, M. Georgieva, Physiology, Bulgarian Academy of Sciences, Sofa, Bulgaria
in
S. Todorov. Institute of 23 G. Bonchev St., 1113
Investigations on effects of time varying field stimulation on the diurnal locomotor learning processes of Syrian hamster
MS did not cause worsening of learning fastness measured with trials creating associations in Skier’s box. In all parameters of stimulation applied acceleration of learning process was observed, but only higher magnetic field evoked statistically significant effect. MS caused emotional changes in animals (diminished number of defecations, urinations and lowered level of aggressiveness of animals exposed to magnetic field stimulation). Conclusions: MS does not evoke any deterioration symptoms of such ens functions as locomotor activity and learning processes. References
Tyr-MIF-I is a naturally occurring endogenous tetrapeptide (Tyr-ProLeu-Gly-NH2) which is a member of the MlF’s family. The intraperitoneal (i.p.) administration of Tyr-MIF-1 produces analgesia that is, at least partly, realized by activation of opioid p-receptors. Clonidine (CLO), an az-adrenoceptor agonist, also exerts an analgesic effect and potentiates the antinociceptive action of opioids, probably affecting common central neuronal pathways, but activating different receptors. In our experiments we studied the effects of an a2-agonist (CLO) and antagonist (yohimbine - YOH) on the nociceptive action of Tyr-MIF-1 in the paw-pressure (PP) test on rats. CL0 (4 mgikg, i.p.) increased the pain threshold of the PP response, while YOH (1 m&g, i.p.) was without effect on the basal nociception (the values of the control animals). The antinociceptive effect of CL0 was stable throughout the experiment duration (l@ min-120” min). The analgesic action of 1 m&g Tyr-MIF-1 was transient, reaching its maximum at the 15” min and disappearing at the 120” min. Coadministrated, Tyr-MIF-1 and CL0 evoked a strong and long-lasting (to the end of the experiment) increase in the pain threshold. YOH suppressed, but did not abolish the Tyr-MIF-l-induced analgesia. The antinociceptive effect of the combination YOH + Tyr-MIF-1 remained stronger that in the controls for 120 min. Pretreatment of the animals with desipramine, an inhibitor of the noradrenaline re-uptake, potentiated the Tyr-MIF-1 analgesic effect. The present results show that the adrenergic neurotransmission can modulate the b-receptor-mediated antinociceptive effect of Tyr-MIF-1. This study was supported by Grant B-601 of the NSF, Bulgaria.
(B-391
Studies
magnetic activity
and
T. Zyss’, B. D+browska*, K. Zajgc*, M. Walczyk*, M. Markiewicz*, B. Witusik*. ‘Department of Psychiatry, Medical College, Jagellonian University; ‘Department of Zoopsychology and Animal Etholog, Jagellonian Universify KraMw, Poland Objective: There are many experimental studies on animals that confirm antidepressive activity of rTMS technique. There are no researches on other effects of magnetic stimulation (MS) available. Method: We have examined the influence of prolonged repetitive MS (B = 0.01-0.15 T, f = 50, 70 and 100 Hz, t = 3@-60 min), and shame stimulation, on diurnal locomotor activity and learning processes in males of Syrian hamster (ntoUl = 120). Both groups of animals received 8-10 stimulation sessions. The examination included several experiments in which various parameters of generated magnetic field (induction and frequency) were applied. Electromagnetic actometers were used to measure the locomotor activity - all day and night long and every day and night of the experiment. Modified Skinner box was used to measure of learning process fastness. General behavioral assessment of animals was made before and after procedure of stimulation and shame stimulation. Results: Applied impulse magnetic field stimulation did not interfere the pattern (phase) of the Syrian hamster diurnal activity rhythm. However, MS lowered the general locomotor activity of animals. Lowering of locomotor activity in stimulated hamsters took place during rest phase (day), during the time of maximum activity (night; dark phase) the influence of the magnetic field were not observed. The effect depended on the field intensity (general exposition, dose).
[l] Dura G.Y., Csorba E.: Experimental study on the influence of pulsating electromagnetic field on motor activity. Bioelecticity 1988, 7, 133-135. [2] Thomas J.R., S&rot J., Liboff A.R.: Low-intensity magnetic fields alter operant behavior in rats. Bioelectromagnetics 1986, 7, 349-357.
IB-401
The diurnal locomotor activity, general behavior learning processes in mice exposed to magnetic stimulation
and field
T. Zyss’, B. Dgbrowska*, K. Zajsc*, B. Bryzek*, M. Kuros*, M. Tabo?. [Department of Psychiatry, Medical College, Jagellonian University; ‘Department of Zoopsychology and Animal Ethologv. Jagellonian University, Krakow, Poland Objective: Biological effects of exposition to magnetic field on living organisms are not entirely known. As clinical magnetic stimulation is applied both diagnostically and therapeutically (e.g. rTMS in treating depression), basic experimental studies on behavioral and biochemical activity of MS (acute and chronic treatment) seem very important. Method: About 600 male mice were exposed to prolonged repetitive MS (B = 0.01-0.15 T, f = 20, 50, 80 and 100 Hz, t = 30-120 min) and shame stimulation. Magnetic stimulation was administered for 8-10 consecutive days. The examination consisted of several experiments with various parameters of induction and frequency of generated magnetic field. The diurnal locomotor activity, general behavior and learning processes were examined. Animal motor activity was measured by electromagnetic actometer; Labyrinth-Test - to observe learning processes; “Open Field”Test - to examine mice emotionality and general behavior. Results: MS applied in mice did not disturb the twenty-four hours motor activity pattern (phase). Some parameters of stimulation changed motor activity (lowered activity, changed phase etc.), but the effect was temporary and maintained for l-2 days. According to Labyrinth-Test, magnetic field did not cause worsening of the learning fastness. Some parameters (B = 0.15 T, f = 80 Hz, t = 30 min, n = 8 days) even shortened the time needed to go through the labyrinth and caused that mice made fewer mistakes. “Open Field”-Test showed statistically significant differences between stimulation with the field of the lowest induction 0.01 T. 1 hour stimulation administered for eight days caused some activation of animals. The activation was measured with the number of approaches to food. Prolonged expositions (2 hours a day) caused reverse effect. Number of approaches to food diminished (with minimally increased number of defecations). Conclusions: The experiments did not confirm threats regarding harmful influence of MS on central nervous system. It neither disturbed memory processes, nor changed general motor activity. Various (unstable) effects were observed regarding its influence on emotionality of animals. References
[l] Dura G.Y., Csorba E.: Experimental study of the influence of pulsating electromagnetic field on motor activity. Bioelectricity 1988, 7, 133-135. [2] Smith R.F., Clarke R.L., Justesen D.R.: Behavioral sensitivity of rats to extremely-low-frequency magnetic fields. Bioelectiomagnetics 1994, 15, 41 l426.
ElB-35
Effect of tramadol analgesia
and
clonidine
on stress-induced
I. Panocka, B. Antkowiak, M. Kowalczyk. Department Military
Institute
of Hygiene
and Epidemiology,
of Pharmacology, Warsaw, Poland
Tramadol is a centrally acting, synthetic analgesic with opioid agonist properties. Experimental data suggest that tramadol may exert part of its analgesic effect through the activation of central inhibitory rnonoaminergic pathways. Systemically administered antagonists of noradrenergic and serotonergic receptors block the antinociception of spinally administered tramadol, but not morphine in the rat tail-flick test. Clonidine is a selective alpha2 adrenergic agonist which shows marked analgesic activity after spinal administration. In our experiments, we studied analgesic properties of tramadol together with systemically administered clonidine before and after stress using tail-immersion test. The experiments were performed on adult male Wistar rats weighing 250-350 g with reversed light/dark cycle. The tail-withdrawal latency following immersion in hot water (55’ C) was measured before and 2, 30 and 60 minutes afier stress (3 min. swimming in water at 20” C). Rats received intraperitoneal injections of tramadol (20 mgkg) or clonidine (50 Kg/kg) or tramadol co-injected with clonidine at the same doses 30 min. before stress. The control group received aqua pro iniectione. The results were expressed as percentage of maximal possible effect (% MPE) according to the formula: (postdrug latency - baseline latency)/(cut-off time - baseline latency) x 100%. Statistically significant differences between the groups analysed were determined using t-test. Before the swimming stress,both tramadol and clonidine given separately and injected together revealed a statistically significant analgesic effect in comparison with the control group. The analgesic effect of tramadol co-injected with clonidine was significantly greater than in the case of the drugs given separately. After stress tramadol together with clonidine produced a significant analgesic effect at minute 2 and 30, tramadol given separately - only at min. 2 and clonidine had no significant effect. Just after the stress,there was no difference between the efficacy of tramadol alone and tramadol together with clonidine. In our experiment the activation of alphal-adrenergic receptors potentiated the analgesic effect of tramadol before and 30 min. after but not just after stress. References [l]
Raffa, R.B. et al., 1992. Opioid and non-opioid mechanisms of action of tramadol, an ‘atypical’ analgesic. J. Pharmacol. Exp. Ther. 260, 275-85. [2] Desmeules, J.A., Pigwt, V., Collart, L., Dayer, P, 1996. Contributin of monoaminergic modulation to the analgesic effect of tramadol. Br. J. Clin. Pharmacol. 41, 7-12.
18-361
Involvement antinociceptlve
of histamlnergic system effect of Tyr-MIF-1
in the
A. Bocheva’, R. Zamfirova’ , W. Scbunack’, S. Todorov’ *. ‘Institute
of Physiology Bulgarian Academy of Science, 23 Acad. G. Bonchev St., I I I3 Sofia. Bulgaria ‘Institut ftir Pharmazie, Freie Universitiit, Kiinigin-Luise-Spaye 2 + 4, I4195 Berlin, Germany
Tyr-MIF-1 is a representative of the MlF’s family of endogenous peptides. It has been isolated from bovine hypothalamus and human parietal cortex that suggests its involvement in nociception. Tyr-MIF- 1 can bind to the p-receptors as well as to its specific non-opiate receptors in the brain. Data in the literature rise the idea that histamine (HA), a well known nociceptive agent, and ‘I@MIF-1 might have a common pathway in their effects on nociception. We tested that possibility by investigating the combined action of FUB 94 (a precursor of the H3-agonist R-amethyl histamine) and Tyr-MIF-1 on nociception. The changes in the
s33
Studies
nociceptive effects were examined in male Wistar rats by the RandallSellito paw-pressure (PP) test, using an analgesimeter (Ugo Basile). A pressure was applied to the hind paw and its magnitude (in g) required to elicit nociceptive responses (squeak and struggle) was taken as the mechanical nociceptive threshold. A cut-off value of 500 g was used to prevent damage of the paw. Tyr-MiF-1 in a dose of 1 mg/kg exerted a strong naloxone-reversible analgesic effect. FUB 94 (5 mg/kg, i.p.) had an antinociceptive action, too. The co-administration of Tyr-MIF1 and FUB 94 increased the antinociceptive effect of the H3-agonist precursor. This effect was reversed when methylene blue (MB, 500 pg/rat) was applied 1 hour before the combination. The results obtained confhmed the hypothesis that second messengers might be involved in the realization of the nociceptive effects of both HA and Tyr-MIF- 1. This study was supported by Grant B-601 of the NSF, Bulgaria. 16-371
Participation antinocicedive oxaprotilik mice
of opioid mechanism on the effect induced bv (+I- and I-)in two behavioural pain’ tests in-
A. WesoIowska, J. Borycz. Institute of Sciences,
12 Sm@na Street, Krakow,
of Pharmacology, Poland
Polish
Academy
Oxaprotiline (OXA), a hydroxy derivative of maprotiline, has two optic isomers which exert an antidepressant action in patients (Delini-Stola et al., 1988). (+)-OXA is a highly selective noradrenaline uptake inhibitor, while (-)-OXA is devoid of such an activity (Waldmeier et al., 1982). The mechanism of clinical action of (-)-OXA has not been elucidated, as yet. Irrespective of its antidepressant activity, (+)-Ox4 produces antinociceptive effects in mice (Gray et al., 1998), however no studies of this type have been conducted for (-)-OXA. The purpose of the present study was to assess the activity of both OXA enantiomers in two experimental models of pain in mice, a hot plate (HPL) test and a writhing syndrome (WS) induced by phenylbenzoquinone, and to determine whether the opioidergic system may be engaged in their antinociceptive effects. Both OXAs were administered intraperitoneally to mice 1 h before the test. Administration of (+)-OXA (0.31-20 m&g) and (-)-OXA (20 m&g) produced a statistically significant elevation of the nociceptive threshold, measured by the increased latencies in the HPL test. Moreover, (+)-OXA (0.62-20 mg/kg) and (-)-enantiomer (5-20 m&g) decreased the number of writhing episodes induced by phenylbenzoquinone in mice. The analgesic effect induced by (+)-OXA (0.31 mg/kg) in the HPL test in mice was abolished by naloxone (2 mgkg, subcutaneously), an opioid antagonist. In the WR test, naloxone (2 m&g) partially, but not significantly, reduced the antinociceptive responses induced by (+)-OXA (0.62 m&g). The antinociceptive action of (-)-OXA (20 mgikg in the HPL test, or 5 mgikg in the WS test) was practically blocked by naloxone
(2 NW.
Naloxone given alone (2 m&g) 10 min before the test did not affect the nociceptive responses in comparison with the effect observed in animals receiving saline in both the tests used. The obtained results show that both OXA enantiomers produce antinociception in the HPL and the WR tests in mice, (+)-enantiomer (a noradrenaline uptake inhibitor) being more effective than (-)-OXA in either test. The endogenous opioid system seems to be implicated, at least partially, in their antinociceptive action. Possible participation of other neurotransmitter systems in the antinociceptive responses induced by both OXA enantiomers will be fhe aim of our further studies. References [l]
Delini-Stala, A., Vassout, A., Hanser, K., Bittiger, H., Buch, O., Olpe, H.R. (1988) Oxaprotiline and its enantiomcrs: do they open new avenues in the research on the mode of action of antidepressants? In: Usdin, E., Goldstein, M., Friedhoff, A., Georgotal, A. (eds.) Frontiers in Neuropsychiatric Research, Macmillan, London, pp. 121-134. [2] Gray, A.M., Spencer, W.J., Sewll, R.D.E. (1998) The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds. Br. J. Pharmacol. 124,669-674.
s34
B. Preclinical
[3] Waldmeier,
P., Bauman, P., Hauser, H., Maitre, L., Storni, A. (1982) Oxaprotiline, a noradrenaline uptake inhibitor with an active and inactive enantiomer. B&hem. Pharmacol. 31, 2169-2176
m
Involvement nociceptive
of adrenergic neurotransmission activity of Tyr-MIF-1
A. Bocheva, R. Zamlirova’, M. Georgieva, Physiology, Bulgarian Academy of Sciences, Sofa, Bulgaria
in
S. Todorov. Institute of 23 G. Bonchev St., 1113
Investigations on effects of time varying field stimulation on the diurnal locomotor learning processes of Syrian hamster
MS did not cause worsening of learning fastness measured with trials creating associations in Skier’s box. In all parameters of stimulation applied acceleration of learning process was observed, but only higher magnetic field evoked statistically significant effect. MS caused emotional changes in animals (diminished number of defecations, urinations and lowered level of aggressiveness of animals exposed to magnetic field stimulation). Conclusions: MS does not evoke any deterioration symptoms of such ens functions as locomotor activity and learning processes. References
Tyr-MIF-I is a naturally occurring endogenous tetrapeptide (Tyr-ProLeu-Gly-NH2) which is a member of the MlF’s family. The intraperitoneal (i.p.) administration of Tyr-MIF-1 produces analgesia that is, at least partly, realized by activation of opioid p-receptors. Clonidine (CLO), an az-adrenoceptor agonist, also exerts an analgesic effect and potentiates the antinociceptive action of opioids, probably affecting common central neuronal pathways, but activating different receptors. In our experiments we studied the effects of an a2-agonist (CLO) and antagonist (yohimbine - YOH) on the nociceptive action of Tyr-MIF-1 in the paw-pressure (PP) test on rats. CL0 (4 mgikg, i.p.) increased the pain threshold of the PP response, while YOH (1 m&g, i.p.) was without effect on the basal nociception (the values of the control animals). The antinociceptive effect of CL0 was stable throughout the experiment duration (l@ min-120” min). The analgesic action of 1 m&g Tyr-MIF-1 was transient, reaching its maximum at the 15” min and disappearing at the 120” min. Coadministrated, Tyr-MIF-1 and CL0 evoked a strong and long-lasting (to the end of the experiment) increase in the pain threshold. YOH suppressed, but did not abolish the Tyr-MIF-l-induced analgesia. The antinociceptive effect of the combination YOH + Tyr-MIF-1 remained stronger that in the controls for 120 min. Pretreatment of the animals with desipramine, an inhibitor of the noradrenaline re-uptake, potentiated the Tyr-MIF-1 analgesic effect. The present results show that the adrenergic neurotransmission can modulate the b-receptor-mediated antinociceptive effect of Tyr-MIF-1. This study was supported by Grant B-601 of the NSF, Bulgaria.
(B-391
Studies
magnetic activity
and
T. Zyss’, B. D+browska*, K. Zajgc*, M. Walczyk*, M. Markiewicz*, B. Witusik*. ‘Department of Psychiatry, Medical College, Jagellonian University; ‘Department of Zoopsychology and Animal Etholog, Jagellonian Universify KraMw, Poland Objective: There are many experimental studies on animals that confirm antidepressive activity of rTMS technique. There are no researches on other effects of magnetic stimulation (MS) available. Method: We have examined the influence of prolonged repetitive MS (B = 0.01-0.15 T, f = 50, 70 and 100 Hz, t = 3@-60 min), and shame stimulation, on diurnal locomotor activity and learning processes in males of Syrian hamster (ntoUl = 120). Both groups of animals received 8-10 stimulation sessions. The examination included several experiments in which various parameters of generated magnetic field (induction and frequency) were applied. Electromagnetic actometers were used to measure the locomotor activity - all day and night long and every day and night of the experiment. Modified Skinner box was used to measure of learning process fastness. General behavioral assessment of animals was made before and after procedure of stimulation and shame stimulation. Results: Applied impulse magnetic field stimulation did not interfere the pattern (phase) of the Syrian hamster diurnal activity rhythm. However, MS lowered the general locomotor activity of animals. Lowering of locomotor activity in stimulated hamsters took place during rest phase (day), during the time of maximum activity (night; dark phase) the influence of the magnetic field were not observed. The effect depended on the field intensity (general exposition, dose).
[l] Dura G.Y., Csorba E.: Experimental study on the influence of pulsating electromagnetic field on motor activity. Bioelecticity 1988, 7, 133-135. [2] Thomas J.R., S&rot J., Liboff A.R.: Low-intensity magnetic fields alter operant behavior in rats. Bioelectromagnetics 1986, 7, 349-357.
IB-401
The diurnal locomotor activity, general behavior learning processes in mice exposed to magnetic stimulation
and field
T. Zyss’, B. Dgbrowska*, K. Zajsc*, B. Bryzek*, M. Kuros*, M. Tabo?. [Department of Psychiatry, Medical College, Jagellonian University; ‘Department of Zoopsychology and Animal Ethologv. Jagellonian University, Krakow, Poland Objective: Biological effects of exposition to magnetic field on living organisms are not entirely known. As clinical magnetic stimulation is applied both diagnostically and therapeutically (e.g. rTMS in treating depression), basic experimental studies on behavioral and biochemical activity of MS (acute and chronic treatment) seem very important. Method: About 600 male mice were exposed to prolonged repetitive MS (B = 0.01-0.15 T, f = 20, 50, 80 and 100 Hz, t = 30-120 min) and shame stimulation. Magnetic stimulation was administered for 8-10 consecutive days. The examination consisted of several experiments with various parameters of induction and frequency of generated magnetic field. The diurnal locomotor activity, general behavior and learning processes were examined. Animal motor activity was measured by electromagnetic actometer; Labyrinth-Test - to observe learning processes; “Open Field”Test - to examine mice emotionality and general behavior. Results: MS applied in mice did not disturb the twenty-four hours motor activity pattern (phase). Some parameters of stimulation changed motor activity (lowered activity, changed phase etc.), but the effect was temporary and maintained for l-2 days. According to Labyrinth-Test, magnetic field did not cause worsening of the learning fastness. Some parameters (B = 0.15 T, f = 80 Hz, t = 30 min, n = 8 days) even shortened the time needed to go through the labyrinth and caused that mice made fewer mistakes. “Open Field”-Test showed statistically significant differences between stimulation with the field of the lowest induction 0.01 T. 1 hour stimulation administered for eight days caused some activation of animals. The activation was measured with the number of approaches to food. Prolonged expositions (2 hours a day) caused reverse effect. Number of approaches to food diminished (with minimally increased number of defecations). Conclusions: The experiments did not confirm threats regarding harmful influence of MS on central nervous system. It neither disturbed memory processes, nor changed general motor activity. Various (unstable) effects were observed regarding its influence on emotionality of animals. References
[l] Dura G.Y., Csorba E.: Experimental study of the influence of pulsating electromagnetic field on motor activity. Bioelectricity 1988, 7, 133-135. [2] Smith R.F., Clarke R.L., Justesen D.R.: Behavioral sensitivity of rats to extremely-low-frequency magnetic fields. Bioelectiomagnetics 1994, 15, 41 l426.