首页>
外文期刊>european journal of neuroscience
>Deficient Sensorimotor Gating After 6‐Hydroxydopamine Lesion of the Rat medial Prefrontal Cortex is Reversed by Haloperidol
【24h】
Deficient Sensorimotor Gating After 6‐Hydroxydopamine Lesion of the Rat medial Prefrontal Cortex is Reversed by Haloperidol
展开▼
机译：Deficient Sensorimotor Gating After 6‐Hydroxydopamine Lesion of the Rat medial Prefrontal Cortex is Reversed by Haloperidol
AbstractThe present study sought to test the hypothesis that dopamine in the prefrontal cortex exerts an inhibitory influence on subcortical dopamine systems and that depletion of prefrontal dopamine may affect behaviour via an increase in dopamine release in the basal ganglia. We used prepulse inhibition of the acoustic startle response, i.e. the inhibition of the acoustic startle response by a preceding non‐startling stimulus, as the behavioural test, because this phenomenon of sensorimotor gating is modified in opposite directions by dopamine in the prefrontal cortex and in the basal ganglia. Rats were tested for prepulse inhibition before and after injections of the neurotoxin 6‐hydroxydopamine into the medial prefrontal cortex. We attempted to differentiate the contributions of prefrontal dopamine and noradrenaline by pretreating the animals with desipramine (6‐OHDADMIrats) or bupropion (6‐OHDABUPrats), selective inhibitors of noradrenaline and dopamine reuptake respectively. 6‐Hydroxydopamine lesion reduced prefrontal dopamine by 90 and noradrenaline by 80 in 6‐OHDADMIrats, while prefrontal dopamine was reduced by 54 and noradrenaline by 95 in 6‐OHDABUPrats. The ability of an acoustic prepulse (75 dB, 10 kHz) to inhibit the response to a startle pulse (100 dB noise burst) was maintained in sham‐lesioned rats and in 6‐OHDABUPrats. However, there was a marked reduction of prepulse inhibition (by 26) in the 6‐OHDADMIrats. Systemic administration of the dopamine antagonist haloperidol (0.05 mg/kg), which did not affect prepulse inhibition in sham‐lesioned and in 6‐OHDABUPrats, antagonized the lesion‐induced deficit in prepulse inhibition in 6‐OHDADMIrats. These results suggest that prefrontal dopamine is involved in prepulse inhibition of the acoustic startle response. The haloperidol‐induced antagonism of the deficit in prepulse inhibition observed in 6‐OHDADMIrats is compatible with the view that prefrontal dopamine depletion led to overactivity of subcortical dopamine systems involved in prepulse inhibition, i.e. in the nucleus accumbens and/or anteromedial striatum. The significance of prefrontal noradrenaline depletion, which may have partially counteracted the effects of dopamine depletion on prepulse inhibition, is also discussed. Since prepulse inhibition is impaired in schizophrenics, the present findings lend support to the theory of prefrontal dopamine hypofunction in
展开▼
