T-type calcium cha
nnels are importa
nt i
n burst firi
ng a
nd expressed i
n brai
n regio
ns implicated i
n schizophre
nia. Therefore, we exami
ned the effects of
novel selective T-type calcium cha
nnel a
ntago
nists i
n precli
nical assays predictive of a
ntipsychotic-like activity. TTA-A2 blocked the psychostimula
nt effects of amphetami
ne a
nd MK-801 a
nd decreased co
nditio
ned avoida
nce respo
ndi
ng. These effects appeared mecha
nism based, rather tha
n compou
nd specific, as two structurally dissimilar T-type a
ntago
nists also reduced amphetami
ne-i
nduced psychomotor activity. Importa
ntly, the ability to reduce amphetami
ne¡¯s effects was mai
ntai
ned followi
ng 20 days pre-treatme
nt with TTA-A2. To explore the
neural substrates mediati
ng the observed behavioral effects, we exami
ned the i
nflue
nce of TTA-A2 o
n amphetami
ne-i
nduced c-
fos expressio
n as well as basal a
nd stimula
nt-evoked dopami
ne a
nd glutamate release i
n?the?
nucleus accumbe
ns. TTA-A2 decreased amphetami
ne-i
nduced c-
fos expressio
n as well as MK-801-i
nduced, but
not basal, glutamate levels i
n the
nucleus accumbe
ns. Basal, amphetami
ne- a
nd MK-801-i
nduced dopami
ne efflux was altered. These fi
ndi
ngs suggest that T-type calcium cha
nnel a
ntago
nism could represe
nt a
novel mecha
nism for treati
ng schizophre
nia.
This article is part of a Special Issue entitled ¡®Schizophrenia?