TY - JOUR
T1 - A comparison of the neurochemical and behavioral effects of clenbuterol and desipramine
AU - Finnegan, Kevin T.
AU - Terwilliger, Megan M.
AU - Berger, Philip A.
AU - Hollister, Leo E.
AU - Csernansky, John G.
N1 - Funding Information:
This work was supported m part by PHS Grant MH-03030, The Norris Mental Health Chnlcal Research Center at Stanford (MH-30854), and by the Veterans Adm:mstratIon Hospital, Palo Alto, CA
PY - 1987/2/10
Y1 - 1987/2/10
N2 - Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS β-adrenoceptors and attenuate brain adenylate cyclase activity, β- adrenoceptor agonist may also possess antidepressant properties. We compared the effects of the centrally acting β-adrenoceptor agonist clenbuterol (5, 10 and 35 mg/kg per day), and the combination of propranolol (5 mg/kg per day) and clenbuterol (10 mg/kg per day), with desipramine (15 mg/kg per day) on forced swim test performance and on cortical β-adrenoceptors in rats following 7 days of drug administration. Desipramine (15 mg/kg per day), and clenbuterol (10 and 35 mg/kg per day, but not 5 mg/kg per day) both significantly reduced immobility in the forced swim test. Frontal cortex β-adrenoceptors were significantly down-regulated after desipramine and all 3 doses of clenbuterol. The co-administration of propranolol (5 mg/kg per day) blocked both the reduction in immobility and down-regulation of cortical β-adrenoceptors induced by clenbuterol (10 mg/kg per day). Propranolol (5 mg/kg per day) alone up-regulated frontal cortex β-adrenoceptors, but had no significant effect on swimming performance. These data suggest that the physiological consequences of β-adrenoceptors down-regulation are important in the mechanism of action of antidepressants. The results also suggest that clenbuterol may be useful in the treatment of depression.
AB - Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS β-adrenoceptors and attenuate brain adenylate cyclase activity, β- adrenoceptor agonist may also possess antidepressant properties. We compared the effects of the centrally acting β-adrenoceptor agonist clenbuterol (5, 10 and 35 mg/kg per day), and the combination of propranolol (5 mg/kg per day) and clenbuterol (10 mg/kg per day), with desipramine (15 mg/kg per day) on forced swim test performance and on cortical β-adrenoceptors in rats following 7 days of drug administration. Desipramine (15 mg/kg per day), and clenbuterol (10 and 35 mg/kg per day, but not 5 mg/kg per day) both significantly reduced immobility in the forced swim test. Frontal cortex β-adrenoceptors were significantly down-regulated after desipramine and all 3 doses of clenbuterol. The co-administration of propranolol (5 mg/kg per day) blocked both the reduction in immobility and down-regulation of cortical β-adrenoceptors induced by clenbuterol (10 mg/kg per day). Propranolol (5 mg/kg per day) alone up-regulated frontal cortex β-adrenoceptors, but had no significant effect on swimming performance. These data suggest that the physiological consequences of β-adrenoceptors down-regulation are important in the mechanism of action of antidepressants. The results also suggest that clenbuterol may be useful in the treatment of depression.
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U2 - 10.1016/0014-2999(87)90158-0
DO - 10.1016/0014-2999(87)90158-0
M3 - Article
C2 - 3032650
AN - SCOPUS:0023127068
VL - 134
SP - 131
EP - 136
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -