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Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration.

Deupree JD, Burke WJ, Bylund DB - BMC Pharmacol. (2008)

Bottom Line: Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose.In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats.

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Affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800 USA. jddeupre@unmc.edu

ABSTRACT

Background: The effects of acute and repeated treatment with desipramine on the functional response of alpha2-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an alpha2-adrenoceptor agonist. The change in the extent of the brimonidine-induced hypothermia following pretreatment with either single or 4 twice-daily injections of desipramine was compared in 13-day old and adult (65-75 days old) male rats.

Results: Brimonidine, alone, lowered rectal temperature to a greater extent in juvenile than in adult rats, and this response was dose-dependently blocked by the selective alpha2-adrenoceptor antagonist, RX821002, in both groups of rats. Single desipramine administration lowered rectal temperature in the absence of brimonidine in adult but not in juvenile rats. The adult rats developed tolerance to this hypothermic effect after 4 days of desipramine treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.

Conclusion: The results suggest that juvenile rats response differently than adult rats to agonist stimulation of alpha2-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the alpha2-adrenoceptor-induced hypothermic effect in juvenile rats is greater than in adult rats. Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats. In addition, the increased alpha2-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.

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Brimonidine induced changes in rectal temperature after 4-days of desipramine treatment in adult rats. Rats were injected twice a day for four days with 10 mg/kg desipramine (DMI) or vehicle starting in either the morning or the evening. Measurements of rectal temperature were conducted the same time each morning 14, 24, 48 and 96 h after the last desipramine/water dose. The rectal temperature was taken immediately prior (0 time) to giving brimonidine (1.0 mg/kg) and then 30, 60, 90 and 120 min thereafter. Data points are the average change in rectal temperature from the zero time temperature for each group of rats. The number of rats used in the 14, 24, 48 and 96 h experiments were 4, 12,14 and 8 control and 4, 12, 13 and 7 desipramine treated rats, respectively. Change in temperature with drug concentration is statistically different (P < 0.05) 24 hr after the last dose. The change in rectal temperature with time is statistically significant (P < 0.001) for all experiments.
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Figure 4: Brimonidine induced changes in rectal temperature after 4-days of desipramine treatment in adult rats. Rats were injected twice a day for four days with 10 mg/kg desipramine (DMI) or vehicle starting in either the morning or the evening. Measurements of rectal temperature were conducted the same time each morning 14, 24, 48 and 96 h after the last desipramine/water dose. The rectal temperature was taken immediately prior (0 time) to giving brimonidine (1.0 mg/kg) and then 30, 60, 90 and 120 min thereafter. Data points are the average change in rectal temperature from the zero time temperature for each group of rats. The number of rats used in the 14, 24, 48 and 96 h experiments were 4, 12,14 and 8 control and 4, 12, 13 and 7 desipramine treated rats, respectively. Change in temperature with drug concentration is statistically different (P < 0.05) 24 hr after the last dose. The change in rectal temperature with time is statistically significant (P < 0.001) for all experiments.

Mentions: Rats that had been treated either acutely or for four days with desipramine (same animals as those in Fig. 4–5) were decapitated under isoflurane anesthesia at the completion of the hypothermic experiment (3 to 4 h after giving brimonidine) and the desipramine concentration ± S.E.M. in the cerebellum was determined. The time given in the table is the time after the last dose of desipramine. Thus the 27 hour data in this table, for example, come from the same animals as the 24 hour data in Fig. 4. The number of rats in each group is given in the legends for Fig. 1–3.


Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration.

Deupree JD, Burke WJ, Bylund DB - BMC Pharmacol. (2008)

Brimonidine induced changes in rectal temperature after 4-days of desipramine treatment in adult rats. Rats were injected twice a day for four days with 10 mg/kg desipramine (DMI) or vehicle starting in either the morning or the evening. Measurements of rectal temperature were conducted the same time each morning 14, 24, 48 and 96 h after the last desipramine/water dose. The rectal temperature was taken immediately prior (0 time) to giving brimonidine (1.0 mg/kg) and then 30, 60, 90 and 120 min thereafter. Data points are the average change in rectal temperature from the zero time temperature for each group of rats. The number of rats used in the 14, 24, 48 and 96 h experiments were 4, 12,14 and 8 control and 4, 12, 13 and 7 desipramine treated rats, respectively. Change in temperature with drug concentration is statistically different (P < 0.05) 24 hr after the last dose. The change in rectal temperature with time is statistically significant (P < 0.001) for all experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2572591&req=5

Figure 4: Brimonidine induced changes in rectal temperature after 4-days of desipramine treatment in adult rats. Rats were injected twice a day for four days with 10 mg/kg desipramine (DMI) or vehicle starting in either the morning or the evening. Measurements of rectal temperature were conducted the same time each morning 14, 24, 48 and 96 h after the last desipramine/water dose. The rectal temperature was taken immediately prior (0 time) to giving brimonidine (1.0 mg/kg) and then 30, 60, 90 and 120 min thereafter. Data points are the average change in rectal temperature from the zero time temperature for each group of rats. The number of rats used in the 14, 24, 48 and 96 h experiments were 4, 12,14 and 8 control and 4, 12, 13 and 7 desipramine treated rats, respectively. Change in temperature with drug concentration is statistically different (P < 0.05) 24 hr after the last dose. The change in rectal temperature with time is statistically significant (P < 0.001) for all experiments.
Mentions: Rats that had been treated either acutely or for four days with desipramine (same animals as those in Fig. 4–5) were decapitated under isoflurane anesthesia at the completion of the hypothermic experiment (3 to 4 h after giving brimonidine) and the desipramine concentration ± S.E.M. in the cerebellum was determined. The time given in the table is the time after the last dose of desipramine. Thus the 27 hour data in this table, for example, come from the same animals as the 24 hour data in Fig. 4. The number of rats in each group is given in the legends for Fig. 1–3.

Bottom Line: Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose.In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800 USA. jddeupre@unmc.edu

ABSTRACT

Background: The effects of acute and repeated treatment with desipramine on the functional response of alpha2-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an alpha2-adrenoceptor agonist. The change in the extent of the brimonidine-induced hypothermia following pretreatment with either single or 4 twice-daily injections of desipramine was compared in 13-day old and adult (65-75 days old) male rats.

Results: Brimonidine, alone, lowered rectal temperature to a greater extent in juvenile than in adult rats, and this response was dose-dependently blocked by the selective alpha2-adrenoceptor antagonist, RX821002, in both groups of rats. Single desipramine administration lowered rectal temperature in the absence of brimonidine in adult but not in juvenile rats. The adult rats developed tolerance to this hypothermic effect after 4 days of desipramine treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the alpha2-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.

Conclusion: The results suggest that juvenile rats response differently than adult rats to agonist stimulation of alpha2-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the alpha2-adrenoceptor-induced hypothermic effect in juvenile rats is greater than in adult rats. Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats. In addition, the increased alpha2-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.

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Related in: MedlinePlus