Reproductive Experience Reduces Haloperidol-lnduced Prolactin Secretion in Female Rats

Abstract

The present study examined possible changes in the dopaminergic regulation of prolactin (PRL) secretion which have been reported to occur in reproductively experienced female rats. In the first experiment, female rats which had raised a litter to weaning and age-matched nulliparous controls were ovariectomized and challenged sequentially 2 days apart with a low (0.2 mg/kg) and high (1.0 mg/kg) dose (intravenously) of haloperidol (HAL), a dopamine antagonist. Blood samples were collected via intra-atrial catheters, and plasma samples were assayed for PRL content by radioimmunoassay. Whereas HAL stimulated increases in plasma PRL concentrations in both nulliparous and primiparous animals, significantly higher levels of plasma PRL were present after both doses of HAL in the nulliparous rats. A second experiment investigated the role of lactation in this change in the ability of HAL to stimulate increases in circulating PRL levels. Separate sets of age-matched primiparous (pups removed on day 1 of lactation) and nulliparous rats were challenged with two doses of HAL 2 weeks after gonadectomy. In contrast to 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 lactation, but not pregnancy alone, significantly reduce the ability of HAL to elevate circulating plasma PRL concentrations. Decreased circulating PRL levels in reproductively experienced females, therefore, may result in part from increased endogenous dopaminergic activity/tone.

Modulation of post-coital dopaminergic tone by prior parity

“…1 B and D, respectively). These data confirmed and expanded the notion that the reproductive experience modulated the dopaminergic tone (Bridges et al, 1993;Felicio et al, 1996;Bridges et al, 1997;Hucke et al, 1998Hucke et al, , 2001Byrnes et al, 2001;Sider et al, 2003;. A similar effect was observed in DA response to haloperidol, although the drug was not supposed to produce an increase in DA levels (P<0.05; Fig.…”

“…Reproductive experience also reduces the sensitivity of nonlactating women to the PRL-releasing actions of dopamine antagonist, metoclopramide (Del los Monteros, 1991). The same effect is demonstrated in rats after haloperidol injection (Bridges et al, 1997). These findings have demonstrated that the reproductive experience alters the female's sensitivity to a dopamine antagonist in regulating PRL secretion.…”

“…These data may suggest that reproductive experience lead the dopaminergic systems to present less intense responses, implied perhaps as a consequence of an increase in stability. In addition to these observations on the striatal dopaminergic system, Bridges et al (1997) showed that the haloperidol-induced prolactin secretion was less intense in primiparous than in the nuliparous rats. Furthermore, a prior reproductive experience reduces the sensitivity of non-nursing women to the endocrine action of metochlorpramide (Del los Monteros, 1991), another dopamine antagonist that induces the prolactin secretion.…”

Reproductive experience influences grooming behavior during pregnancy in rats

“…Higher doses of opiates are needed to obtain a drug-induced disruption of maternal behavior in experienced animals. Both basal and drug-induced increases of plasma prolactin levels are lower in cycling parous than in age-matched virgin rats (7,8). Similarly, both opioid-induced release and suckling-stimulated prolactin release are less intense in multiparous than in primiparous rats (4).…”

“…These influences have been demonstrated in various physiological states (7). Particularly during pregnancy, a previous reproductive experience induces changes in both endocrine and neurochemical profile (8,9).…”