TY - JOUR
T1 - Lithium, but not carbamazepine, potentiates hyperactivity induced by intra-accumbens cholera toxin
AU - Kofman, Ora
AU - Li, Peter P.
AU - Warsh, Jerry J.
N1 - Funding Information:
The authors thank Staveroula Andreopoulous and Kin Po Siu for technical assistance and Dr. Paul Fletcher and Dr. Don Coscina for use of their laboratory facilities. This work was supported by a grant from the Ontario Mental Health Foundation to the authors (1995).
PY - 1998/1/1
Y1 - 1998/1/1
N2 - Elevated G protein abundance and/or function has been implicated in the pathophysiology and pharmacotherapy of bipolar affective disorder. To test the interactions between chronic lithium and carbamazepine on behavioral changes induced by cholera toxin (CTX), which catalyzes ADP-ribosylation and constitutively activates Gas/olf, rats were given chronic dietary lithium, carbamazepine (CBZ), or regular food (REG) and injected bilaterally in the nucleus accumbens (nACC) with CTX (400 ng/ml/side) or vehicle. Locomotor activity was tested daily for 2 weeks after the injection. CTX increased locomotor activity, but a significant interaction between drug treatment and CTX reflected a two- to threefold increase of CTX-induced hyperactivity in the lithium-treated group. In contrast, on day 1, the CBZ-CTX group was significantly more active than the the LI-CTX and REG-CTX groups, both of which had suppressed locomotor activity. There was a significant reduction in CTX-catalyzed ADP ribosylation of Gαs (52 kDa and 45 kDa) in the nucleus accumbens in all three CTX-treated groups. The potentiation of the behavioral effect of CTX by lithium supports the hypothesis that lithium interacts with G proteins; however, the mechanism of interaction appears to be more complex than direct attenuation of Gas function, as previously suggested.
AB - Elevated G protein abundance and/or function has been implicated in the pathophysiology and pharmacotherapy of bipolar affective disorder. To test the interactions between chronic lithium and carbamazepine on behavioral changes induced by cholera toxin (CTX), which catalyzes ADP-ribosylation and constitutively activates Gas/olf, rats were given chronic dietary lithium, carbamazepine (CBZ), or regular food (REG) and injected bilaterally in the nucleus accumbens (nACC) with CTX (400 ng/ml/side) or vehicle. Locomotor activity was tested daily for 2 weeks after the injection. CTX increased locomotor activity, but a significant interaction between drug treatment and CTX reflected a two- to threefold increase of CTX-induced hyperactivity in the lithium-treated group. In contrast, on day 1, the CBZ-CTX group was significantly more active than the the LI-CTX and REG-CTX groups, both of which had suppressed locomotor activity. There was a significant reduction in CTX-catalyzed ADP ribosylation of Gαs (52 kDa and 45 kDa) in the nucleus accumbens in all three CTX-treated groups. The potentiation of the behavioral effect of CTX by lithium supports the hypothesis that lithium interacts with G proteins; however, the mechanism of interaction appears to be more complex than direct attenuation of Gas function, as previously suggested.
KW - Bipolar affective disorder
KW - Carbamazepine
KW - Cholera toxin
KW - G protein
KW - Lithium
KW - Locomotor activity nucleus accumbens
UR - http://www.scopus.com/inward/record.url?scp=0031973757&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(97)00410-3
DO - 10.1016/S0091-3057(97)00410-3
M3 - Article
AN - SCOPUS:0031973757
SN - 0091-3057
VL - 59
SP - 191
EP - 200
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -
