Binding of [3H]PD 128907, a putatively selective ligand for the D3 dopamine receptor, in rat brain: a receptor binding and quantitative autoradiographic study.

[3H]PD 128907 has been proposed as a selective ligand for the D3 dopamine receptor. This study characterizes the binding of this radioligand in rat brain using in vitro radioligand binding and autoradiographic methods. In radioligand binding studies, [3H]PD 128907 exhibited 0.3 nmol/L affinity for a single, low density site in ventral striatal membranes. The pharmacological profile for [3H]PD 128907 was similar to that of [3H](+)-7-OH-DPAT with the rank order of potency for dopamine agonists being PD 128907 approximately 7-OH-DPAT approximately quinpirole > or = dopamine; for antagonists, spiperone > (+)-butaclamol approximately domperidone > or = haloperidol > SCH 23390. Guanyl nucleotides had no effect on the binding of either ligand. These observations indicate labeling of a dopaminergic site with characteristics consistent with the D3 receptor. In autoradiographic studies, highest densities of [3H]PD 128907-labeled sites were observed in islands of Calleja followed by the nucleus accumbens, nucleus of the horizontal limb of the diagonal band, the molecular layer of cerebellar lobule X, and the ventral caudate/putamen.

Comparison of D2 and D3 dopamine receptor affinity of dopaminergic compounds in rat brain.

This study used quantitative autoradiography to simultaneously evaluate the relative affinities of dopaminergic compounds for dopamine D2 and D3 receptors in rat brain. PD 152255, PD 128907, and l-nafadotride exhibited significantly higher affinity for cerebellar dopamine D3 sites than [3H]quinpirole-labeled sites in caudate/putamen (6.3-, 6.0-, and 2.3-fold, respectively). In contrast, chlorpromazine, risperidone, and domperidone were more potent at striatal dopamine D2 receptors (3.8-, 31-, and 40-fold, respectively). Dopamine, quinelorane, (+)-UH 232, and RS-trans-7-OH-PIPAT exhibited relatively little D2/D3 selectivity.

Rat placental lactogens initiate and maintain lactation yet inhibit suckling-induced prolactin release.

Mammalian reproduction is dependent on both a successful pregnancy and on the subsequent period of lactation. In the rat, ovulation occurs shortly after parturition making it possible for a dam to be simultaneously pregnant and lactating. The present studies investigate the effect of placental hormones on suckling-induced prolactin (PRL) release and the contribution of placental hormones to milk synthesis and secretion. A rat choriocarcinoma cell line, Rcho-1, which secretes placental lactogens (PLs) following transplantation in vivo, attenuated suckling-induced PRL release on both d 9 and d 14 of lactation by 43 and 58%, respectively. When PRL secretion was completely inhibited by bromocriptine, a dopamine agonist, Rcho-1-bearing dams still maintained a normal litters weight gain, demonstrating that placental lactogens can continue an established lactation. The Rcho-1 tumors also initiated milk synthesis and secretion in nulliparous rats continuously exposed to pups. Whereas none of the 11 control virgins began lactating and had an average pup weight loss of 2.07 g, the Rcho-1-bearing rats began lactating, as evidenced by a significant reduction in pup weight loss. Thirty percent of these rats became fully lactationally competent. Northern blot analysis showed that the Rcho-1 tumors expressed both PL-I and PL-II mRNA in all experimental groups. These tumors also secreted PL-I into the circulation, as shown by radioimmunoassay.