The present study examined possible changes in the dopaminergic regula
tion of prolactin (PRL) secretion which have been reported to occur in
reproductively experienced female rats. In the first experiment, fema
le rats which had raised a litter to weaning and age-matched nulliparo
us controls were ovariectomized and challenged sequentially 2 days apa
rt with a low (0.2 mg/kg) and high (1.0 mg/kg) dose (intravenously) of
haloperidol (HAL), a dopamine antagonist. Blood samples were collecte
d via intra-atrial catheters, and plasma samples were assayed for PRL
content by radioimmunoassay. Whereas HAL stimulated increases in plasm
a PRL concentrations in both nulliparous and primiparous animals, sign
ificantly higher levels of plasma PRL, were present after both doses o
f HAL in the nulliparous rats. A second experiment investigated the ro
le of lactation in this change in the ability of HAL to stimulate incr
eases in circulating PRL levels. Separate sets of age-matched primipar
ous (pups removed on day 1 of lactation) and nulliparous rats were cha
llenged with two doses of HAL 2 weeks after gonadectomy. In contrast t
o the effect of pregnancy and lactation found in the first experiment,
pregnancy and parturition in the absence of lactation failed to alter
the female's sensitivity to HAL. The PRL responses in the two groups
were identical at the low HAL dose and similar after the high HAL dose
. These findings demonstrate that a single prior pregnancy and lactati
on, but not pregnancy alone, significantly reduce the ability of HAL t
o elevate circulating plasma PRL concentrations. Decreased circulating
PRL levels in reproductively experienced females, therefore, may resu
lt in part from increased endogenous dopaminergic activity/tone.