Effects of chronic bromocriptine treatment on tyrosine hydroxylase (TH) mRNA expression, TH activity and median eminence dopamine concentrations in ageing rats

The purpose of this study was to investigate the age-related changes in the responsiveness of tuberoinfundibular dopamine (TIDA) neurones to chronic h ypoprolactinemia induced by treatment with bromocriptine, a dopamine recept or agonist, In one experiment, TIDA neuronal activity after acute hypoprola ctinemia or exogenous prolactin was monitored by measuring tyrosine hydroxy lase (TH) activity in the stalk median eminence of middle-aged cycling fema le rats (10-12 months), old constant oestrous rats (18-20 months) and old p seudopregnant rats (22-24 months). in another experiment, middle-aged cycli ng (10-12 months) rats were treated with bromocriptine for 6 or 12 months. TH activity was measured in the stalk median eminence, TH mRNA levels were measured in the arcuate nucleus and dopamine concentrations were measured i n the arcuate nucleus and median eminence. Responsiveness of TIDA neurones to exogenous prolactin and to the withdrawal of bromocriptine in these rats was also tested. While the TIDA neurones in all three age groups responded to acute hypoprolactinemia by showing a reduction in TH activity, older ra ts failed to respond to exogenous prolactin administration, In contrast, ch ronic hypoprolactinemia for 12 months enabled the rats to retain TIDA neuro nal responsiveness to exogenous prolactin, It also decreased TIDA neuronal function as measured by dopamine concentrations in the median eminence, TH activity in the stalk median eminence and TH mRNA in the arcuate nucleus of ageing rats. The restoration of the responsiveness of these neurones to pr olactin stimulation in older rats demonstrates for the first time that hypo prolactinemia produced by chronic bromocriptine treatment indeed provides a neuroprotective effect on TIDA neurones. These results indicate that maint aining a low level of neuronal activity by lowering prolactin levels may be a contributing factor in retaining the plasticity of TIDA neurones.