Blockade of beta 1- but not of beta 2-adrenergic receptors replicates propranolol's suppression of the cerebral spread of an engram in mice.
Bitemporal injections of puromycin that primarily affect the hippocampal-entorhinal area induce amnesia of aversive maze-learning in mice for 3 days after training but are ineffective 6 or more days after training. At these later times, additional puromycin sites covering widespread forebrain areas are necessary to induce amnesia, a result that we attribute to the cerebral spread of the engram during the 6-day period. We have reported that blockade of about 60% of cerebral beta-adrenergic receptors by a single, subcutaneous injection of (-)-propranolol, a nonselective beta-receptor antagonist, inhibited engram spread for 60-90 days, at which time engram spread spontaneously occurred. In the present experiments using single doses of antagonists that appeared to block 60% of beta 2- or beta 1-adrenergic receptors, it was found that the selective beta 2 antagonist ICI 118,551 was without effect on engram spread, whereas the selective beta 1 antagonist betaxolol inhibited the spread for at least 3 months. Propranolol's effect consequently appears to be accounted for by its blockade of beta 1 receptors.
Flexner
J B
JB
Flexner
L B
LB
Church
A C
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Rainbow
T C
TC
Brunswick
D J
DJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000647:Amnesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D015784:Betaxolol; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002531:Cerebellum / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011691:Puromycin / Q000633:toxicity; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D011691:Puromycin; D011433:Propranolol; D015784:Betaxolol