[Effects of midazolam on muscarinic receptor of brain in healthy and scopolamine-treated rats].
OBJECTIVE
To investigate the recent and permanent effects of pretreatment with midazolam on muscarinic receptor of brain in healthy and scopolamine-treated rats.


METHODS
(1) In recent effect group, thirty-eight male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=10), midazolam+scopolamine group (Mid+sco, n=10). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco groups were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 4th, 5th, and 6th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while same voluminal physiological saline was administered in Con group and Mid group. (2) In permanent effect group, thirty-six male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=9), midazolam+scopolamine group (Mid+sco, n=9). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco group were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 10th, 11th, and 12th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while the same voluminal physiological saline was administered in Con group and Mid group. (3)Then the rats was decapitated and the cerebra cortex and hippocampus were removed. The binding capacity of muscarinic receptor with [3H] QNB were determined. Bmax and Kd of muscarinic receptor in hippocampus were determined by Scatchard analysis in recent effect group.


RESULTS
(1) In recent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group, Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group (P<0.05) and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.01). Kd of muscarinic receptor in hippocampus in Sco group and Mid group were higher than in Con group and Mid+sco group (P<0.01). Bmax of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group (P<0.05), Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.05). There was no significant difference of the binding capacity of muscarinic receptor in cortex. (2) In permanent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group and Mid group than in Sco group and Mid+sco group (P<0.01). There was no significant difference of the binding capacity of muscarinic receptor in cortex.


CONCLUSIONS
Pretreatment with intraperitoneal injection of 50 mg/kg midazolam for three days had no effect on muscarinic receptor of cortex, but could induce the binding capacity of muscarinic receptor with [3H] QNB and change the density and affinity of muscarinic receptor in hippocampus in healthy and scopolamine-treated rats, yet the changes were not permanent.
Zhang
Jie
J
Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China.
Wu
Xin-min
XM
Zuo
Ping-ping
PP
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D012601:Scopolamine; D008874:Midazolam