Haloperidol catalepsy consolidation in the rat as a model of neuromodulatory integration.
Haloperidol, a non-selective D(2) dopamine antagonist, both in vitro (1 microM) and in vivo (2.5 mg/kg i.p.), induced a long-term potentiation of K(+)-induced Ca(2+)-dependent release of endogenous noradrenaline and dopamine in rat brain cortical slices, by increasing the content of noradrenaline and dopamine known to be controlled by dopamine auto- and heteroreceptors. Haloperidol administration (2.5 mg/kg i.p.) evoked catalepsy and increased the content of noradrenaline and dopamine in the same structures of the brain. Haloperidol catalepsy consolidated without any additional learning and could be retrieved up to two weeks later by placing the animals in the test box. The catalepsy is disordered and retrieved only in the test box. The catalepsy was more intense on day 14 than on day 7. Injection of haloperidol immediately after conditioning evened the reflex retrieval on the following days. Moreover, learning increased the intensity of catalepsy in animals tested on the day of injection. Repeated testing of the reflex on the following days led to specific modifications of catalepsy retrieval. Pre-conditioned rats exhibited maximal catalepsy when tested immediately after being placed in the test box. These results suggest that both the processes of long-term potentiation and catalepsy consolidation are mediated by the same type of receptors, long-term modulation-inducing receptors. Endogenous neuromodulators, acting non-specifically or diffusely via their respective long-term modulation-inducing receptors, can initiate and consolidate generalized states which form the basis for emotional and motivational states.
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia. bazyan@mail.ru
A S
AS
Bazyan
V M
VM
Getsova
N V
NV
Orlova
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018492:Dopamine Antagonists; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine