Regional brain metabolic responsivity to the muscarinic cholinergic agonist arecoline is similar in young and aged Fischer-344 rats.
In order to determine whether a functional deficit in brain cholinoception accompanies the reported loss of muscarinic receptors with age, local cerebral glucose utilization (LCGU) was measured in awake 3- and 24-month-old rats after the administration of the muscarinic cholinergic agonist arecoline. Awake, male Fischer-344 rats received isotonic saline or arecoline (0.05-50 mg/kg), i.p., and LCGU was measured in 95 regions with the [14C]2-deoxy-D-glucose technique. Plasma and brain pharmacokinetics of arecoline in rats of both ages were measured in a separate experiment and were found not to differ between the two age groups. Peak cerebral cortex arecoline concentrations, at 3 min after the administration of 5 mg/kg, i.p., were 1558 +/- 588 and 1830 +/- 317 ng/g in 3- and 24-month-old rats, respectively. LCGU effects were dose-dependent, with fewer regions activated by smaller doses. In 24-month-old rats, arecoline in one or more doses elevated LCGU significantly in 94% of the regions examined; no declines in LCGU were found. Increases in whole brain glucose utilization produced by all doses of arecoline, compared to control values, were similar in 3- and 24-month-old rats. After one or more doses, the rise in LCGU in 24-month-old animals, compared to that in 3-month rats, was not significantly different in 75 brain regions, greater in 13 and smaller in 7. These findings demonstrate that the functional responsivity of brain regions to a cholinergic agonist is, for the most part, age-invariant in the rat, implying that the function of muscarinic receptor and postreceptor mechanisms remains intact despite reported age-related losses of muscarinic receptors.
Soncrant
T T
TT
Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892.
Holloway
H W
HW
Greig
N H
NH
Rapoport
S I
SI
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001115:Arecoline / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D011976:Receptors, Muscarinic; D001115:Arecoline; D005947:Glucose