Studies on rat brain catecholamine synthesis and beta-adrenoceptor number following administration of electroconvulsive shock, desipramine and clenbuterol.
The effects of administration to rats of repeated electroconvulsive shock (ECS), clenbuterol and desipramine (DMI) on beta-adrenoceptor number in cortex, and noradrenaline (NA) and dopamine (DA) turnover in whole brain has been investigated by examining the rate of decline of NA concentration (kNA) following injection of alpha-methyl-p-tyrosine. A single injection of clenbuterol (5 mg/kg) raised brain NA content and decreased the rate constant (kNA), leaving the turnover rate unaltered. Acute DMI injection decreased kNA and turnover rate, while a single ECS did not change NA metabolic rate. Repeated treatment with either ECS (5 seizures over 10 days), clenbuterol (5 mg/kg for 14 days) or DMI (5 mg/kg twice daily for 14 days) decreased beta-adrenoceptor density in cortex. No change in NA content, rate constant or turnover rate was observed after repeated ECS or clenbuterol administration. Ninety min after the last dose of DMI brain NA content was significantly decreased but kNA was unchanged compared with control animals, possibly because of the presence of subsensitive presynaptic alpha 2-adrenoceptors. At 18 hours after the last dose brain NA content was still lower than control animals but kNA was enhanced. This presumably a "withdrawal" effect, the uptake inhibitory effect of the drug now being decreased. The treatments had little effect on DA turnover apart from DMI decreasing synthesis rate. Clearly there is no obvious relationship between the ability of antidepressant treatments to alter NA turnover and decrease beta-adrenoceptor number.
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002976:Clenbuterol / Q000008:administration & dosage*; D003891:Desipramine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D004338:Drug Combinations; D004597:Electroshock; D004983:Ethanolamines / Q000008:administration & dosage*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors
D002395:Catecholamines; D004338:Drug Combinations; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; D002976:Clenbuterol