Effects of inhibiting neonatal methamphetamine-induced corticosterone release in rats by adrenal autotransplantation on later learning, memory, and plasma corticosterone levels.
BACKGROUND
Neonatal rat methamphetamine (MA) exposure has been shown to cause long-term behavioral impairments similar to some of those observed following neonatal stress. The mechanism by which MA induces impairments is unknown but may be related to early increases in corticosterone release. We previously developed a method to attenuate MA-induced corticosterone release using adrenal autotransplantation (ADXA) in neonatal rats. This exposure period corresponds to the second-half of human pregnancy.


OBJECTIVE
To determine whether inhibition of neonatal MA-induced increases in corticosterone attenuates the long-term behavioral deficits associated with early MA treatment.


RESULTS
ADXA successfully attenuated MA-induced plasma corticosterone increases by approximately 50% during treatment (P11-20) but did not attenuate the long-term behavioral effects of MA treatment. MA-treated rats, regardless of surgery, showed increased errors and latencies in the Cincinnati water maze test of egocentric learning and increased latency, path length, and cumulative distance in three phases of Morris water maze spatial learning and reference memory. MA-treated offspring were hypoactive, had subtle reductions in anxiety in the elevated zero maze but not in the light-dark test. ADXA had no effect on MA-induced long-term 5-HT reductions in the neostriatum or entorhinal cortex or on 5-HIAA reductions in the hippocampus.


CONCLUSIONS
Fifty percent attenuation of neonatal MA-induced elevations in corticosterone does not alter the long-term egocentric or allocentric learning deficits or other behavioral effects of neonatal MA exposure. Because the ADXA effect was partial, the data cannot rule out the possibility that a more complete block of MA-induced corticosterone release might not prevent later cognitive deficits.
Grace
Curtis E
CE
Division of Neurology, Dept. of Pediatrics, Cincinnati Children's Research Foundation, Cincinnati, OH 45229-3039, United States.
Schaefer
Tori L
TL
Graham
Devon L
DL
Skelton
Matthew R
MR
Williams
Michael T
MT
Vorhees
Charles V
CV
D000311:Adrenal Glands / Q000187:drug effects / Q000637:transplantation*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
D008694:Methamphetamine; D003345:Corticosterone