Roles of neurotransmitter receptors in behavior: recovery of function following decreases in muscarinic receptor density induced by cholinesterase inhibition.
Cholinergic neurotransmitter levels were elevated in rat brain by reducing its inactivating enzyme, acetylcholinesterase (AChE), with an anti-AChE agent. Elevated levels result in decreases in cholinergic (muscarinic) receptors. Withdrawal of agent after 10 days of chronic treatment began a gradual return of neurochemical variables toward normal states, yet not fully achieving them within the following 29 days of the experiment. All behavioral and physiological variables measured showed significant effects at the start of the treatment period, developing tolerance at different rates as treatments continued. They also recovered differentially during withdrawal. Results are consistent with a theoretical model in which thresholds for normal functioning of different behavioral and physiological processes are associated with different receptor densities.
Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024.
R W
RW
Russell
R A
RA
Booth
C A
CA
Smith
D J
DJ
Jenden
M
M
Roch
K M
KM
Rice
S D
SD
Lauretz
D000109:Acetylcholine / Q000502:physiology*; D000110:Acetylcholinesterase / Q000502:physiology; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004361:Drug Tolerance; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D007531:Isoflurophate; D000110:Acetylcholinesterase; D000109:Acetylcholine