TY - JOUR
T1 - Norepinephrine-dependent and independent mechanisms of persistent effects of amphetamine in rat cerebellum
AU - Sorensen, Stephen M.
AU - Hattox, Susan
AU - Johnson, Steven W.
AU - Bickford, Paula
AU - Murphy, Robert
AU - Freedman, Robert
N1 - Funding Information:
This work was supported by USPHS Grants DA-02429 and DA-07043, and funds from the Veterans Administration Medical Service. Dinah Rogers prepared the manuscript.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1985/6/24
Y1 - 1985/6/24
N2 - Previous studies of the effects of chronic low-dose amphetamine (2 mg/kg per day × 21 days) on the spontaneous discharge rate of cerebellar Purkinje neurons have shown persistent depressant effects for up to 50 days after cessation of drug administration. The depression of spontaneous discharge observed was only partially reversible by various pharmacological agents which disrupt noradrenergic neurotransmission in cerebellum. In the present study, several additional approaches were used to investigate further this persistent effect. Rats were treated, either before or after chronic treatment with amphetamine, with intracisternal 6-hydroxydopamine at doses which destroy most noradrenergic fibers in cerebellum. In either case Purkinje neurons were still significantly slowed after cessation of amphetamine treatment, although the depression was not as great as previously observed. In another experiment, cerebellar cortical levels of 3-methoxy, 4-hydroxy phenyl glycol (MHPG) were measured after cessation of amphetamine administration, to determine if there was biochemical evidence for increased noradrenergic neurotransmission. At ten days, MHPG levels were elevated by 36%, and they returned to control values by 30 days. The evidence obtained in these studies suggests that chronic amphetamine treatment causes a persistent increase in noradrenergic neurotransmission, but non-noradrenergic mechanisms may also be important mechanisms in the long-lasting depression of activity of cerebellar Purkinje neurons.
AB - Previous studies of the effects of chronic low-dose amphetamine (2 mg/kg per day × 21 days) on the spontaneous discharge rate of cerebellar Purkinje neurons have shown persistent depressant effects for up to 50 days after cessation of drug administration. The depression of spontaneous discharge observed was only partially reversible by various pharmacological agents which disrupt noradrenergic neurotransmission in cerebellum. In the present study, several additional approaches were used to investigate further this persistent effect. Rats were treated, either before or after chronic treatment with amphetamine, with intracisternal 6-hydroxydopamine at doses which destroy most noradrenergic fibers in cerebellum. In either case Purkinje neurons were still significantly slowed after cessation of amphetamine treatment, although the depression was not as great as previously observed. In another experiment, cerebellar cortical levels of 3-methoxy, 4-hydroxy phenyl glycol (MHPG) were measured after cessation of amphetamine administration, to determine if there was biochemical evidence for increased noradrenergic neurotransmission. At ten days, MHPG levels were elevated by 36%, and they returned to control values by 30 days. The evidence obtained in these studies suggests that chronic amphetamine treatment causes a persistent increase in noradrenergic neurotransmission, but non-noradrenergic mechanisms may also be important mechanisms in the long-lasting depression of activity of cerebellar Purkinje neurons.
UR - http://www.scopus.com/inward/record.url?scp=0022431596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022431596&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(85)90342-X
DO - 10.1016/0024-3205(85)90342-X
M3 - Article
C2 - 3925266
AN - SCOPUS:0022431596
VL - 36
SP - 2383
EP - 2389
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 25
ER -