Psychopharmacological consequences of activation of beta adrenergic receptors by SOM-1122.
SOM-1122 was found to be a high-affinity, partial agonist for beta adrenergic receptors. SOM-1122 inhibited the binding of [125I]iodopindolol to membranes prepared from rat cerebral cortex and cerebellum. GTP regulated the binding of SOM-1122 by increasing the Hill coefficient in both tissues and reducing the affinity of the receptor for SOM-1122 in the cerebellum. SOM-1122 increased the concentration of cyclic AMP in slices of rat cerebral cortex in a dose-dependent manner; this effect was antagonized by propranolol. Two lines of evidence suggested that SOM-1122 was centrally active after peripheral administration. First, SOM-1122 inhibited the binding of [125I]iodopindolol in vivo in a dose-dependent manner. Second, after chronic infusion with SOM-1122 for 7 days, the density of beta adrenergic receptors in the cerebellum was reduced; receptor density also was reduced 18 hr after acute administration of SOM-1122, although to a lesser extent. SOM-1122 was found to be behaviorally active. It reduced locomotor activity and reduced response rate under a multiple fixed-interval, fixed-ratio schedule in a dose-dependent manner. SOM-1122 also reduced response rate and increased reinforcement rate under a differential-reinforcement-of-low-rate schedule. These behavioral actions of SOM-1122 appeared to be due to an interaction of the agonist with beta adrenergic receptors, as they were antagonized by propranolol. The behavioral changes produced by stimulation of beta adrenergic receptors with SOM-1122 were generally similar to those caused by other centrally acting beta adrenergic agonists and by antidepressant drugs.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D011943:Receptors, Adrenergic, beta; C056531:SOM 1122; C029247:3-iodopindolol; D006160:Guanosine Triphosphate; D011433:Propranolol; D010869:Pindolol; D000242:Cyclic AMP