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Modification of cholecystokinin hypothermia after neuroleptic treatment in the rat
Pharma cological Research. Vol. 22. Supplement 2.1990
465
MODIFICATION OF CHOLECYSTOKININ HYPOTHERMIA AFTER NEUROLEPTIC TREAT MENT IN THE RAT Spadaro C., Marrano L., Parenti C., Scoto G.M. and Arrigo Reina R. Inst. of Pharmacology and Pharmacognosy, Vl.A.Doria 6, 95125 CATANIA Cho 1ecys toki ni n-octapept i de (CCK-8) produces s i gnifi cant hypothermi a after it has been administered centrally in rats maintained at an a!!! bient temperature of 22°C,that was enhanced in stressed rats. The main purpose of the present study was to determine whether CCK8-induced hypothermia is dependent on the functional integrity of acknowledged neurotransmitter systems which playa prominent role in thermoregulatory processes. Consequently, we sought to clarify the CCK-8 hypothermic effect by utilizing pharmacological treatment which alter the function of these neurotransmitter systems. Pretreatment of rats with anti-adrenergic (propranolol 2 mg/kg i .p.) or anti - opiate (naloxone 5 mg/kg s.c.) agents did not significantly alter CCK-8 - tn duced hypothermia. On the contrary, surgical ablation of adrenal glands, or dexamethasone - pretreatment, affects CCK-8-induced hYPQ thermia. Temperature regulation is 1inked to hypothalamic monoamines and catecholamine balance has been proposed. Since dopamine mech~ nisms are implicated in the depression of body temperature, in the present study, the role of dopamine, in the mediating the tempera ture changes produced by CCK-8, was also examined by acute and sUQ chronic pretreatment of the animals with haloperidol, a dopamine aD. tagonist, given intraperitoneally at dose of 1 mg/kg. Hypothermic ei fects of CCK-8 did not modify after acute treatment with neuroleptic haloperidol, whereas after subchronic treatment ( 1 mg/kg i .p. daily for two weeks) CCK-8-induced hypothermia was significantly reduced. The present findings, together with the knowledge that rat has a hYPQ thermic dopamine mechanism, and the fact that CCK-8 alter dopamine function,suggest a significant role for dopamine in the hypothermic effect induced by CCK-8 in the rat. Although the data presented in this report, many more studies will have to be carried out to under stand mechanisms underlying hypothermic responses to CCK-8.
I043-{)618/90/22II0465-0 1/S03.00/0
© 1990The Italian Pharmacological Society
465
MODIFICATION OF CHOLECYSTOKININ HYPOTHERMIA AFTER NEUROLEPTIC TREAT MENT IN THE RAT Spadaro C., Marrano L., Parenti C., Scoto G.M. and Arrigo Reina R. Inst. of Pharmacology and Pharmacognosy, Vl.A.Doria 6, 95125 CATANIA Cho 1ecys toki ni n-octapept i de (CCK-8) produces s i gnifi cant hypothermi a after it has been administered centrally in rats maintained at an a!!! bient temperature of 22°C,that was enhanced in stressed rats. The main purpose of the present study was to determine whether CCK8-induced hypothermia is dependent on the functional integrity of acknowledged neurotransmitter systems which playa prominent role in thermoregulatory processes. Consequently, we sought to clarify the CCK-8 hypothermic effect by utilizing pharmacological treatment which alter the function of these neurotransmitter systems. Pretreatment of rats with anti-adrenergic (propranolol 2 mg/kg i .p.) or anti - opiate (naloxone 5 mg/kg s.c.) agents did not significantly alter CCK-8 - tn duced hypothermia. On the contrary, surgical ablation of adrenal glands, or dexamethasone - pretreatment, affects CCK-8-induced hYPQ thermia. Temperature regulation is 1inked to hypothalamic monoamines and catecholamine balance has been proposed. Since dopamine mech~ nisms are implicated in the depression of body temperature, in the present study, the role of dopamine, in the mediating the tempera ture changes produced by CCK-8, was also examined by acute and sUQ chronic pretreatment of the animals with haloperidol, a dopamine aD. tagonist, given intraperitoneally at dose of 1 mg/kg. Hypothermic ei fects of CCK-8 did not modify after acute treatment with neuroleptic haloperidol, whereas after subchronic treatment ( 1 mg/kg i .p. daily for two weeks) CCK-8-induced hypothermia was significantly reduced. The present findings, together with the knowledge that rat has a hYPQ thermic dopamine mechanism, and the fact that CCK-8 alter dopamine function,suggest a significant role for dopamine in the hypothermic effect induced by CCK-8 in the rat. Although the data presented in this report, many more studies will have to be carried out to under stand mechanisms underlying hypothermic responses to CCK-8.
I043-{)618/90/22II0465-0 1/S03.00/0
© 1990The Italian Pharmacological Society