Effect of paraventricular injection of neuropeptide Y on milk and water intake of preweanling rats.

This study investigated the effect of paraventricular nucleus (PVN) injection of neuropeptide Y (NPY) on milk and water intake of 2- and 15-day-old sated rats. On the day prior to testing, rat pups were removed from their mothers and implanted with a cannula directed unilaterally at the PVN. On the following day, each pup was implanted with an intra-oral cannula for oral infusion of milk or water that could be swallowed or rejected. Following a 1-hour period fo satiation, each pup received a PVN injection of saline or a single dose of NPY (23.5-235.0 pmol). Milk or water intake was then assessed in a 1-hour test period. Injection of NPY into the PVN enhanced milk and water intake equally at 2 days of age. At 15 days, NPY produced a significantly greater enhancement of milk than water intake. These findings, which are similar to those observed previously with PVN injections of norepinephrine (NE), suggest that: (1) NPY receptors in the PVN, like alpha 2-noradrenergic receptors, are functional very early in the postnatal development of the rat; (2) NPY, in addition to its orexigenic effect, produces a small but significant dipsogenic effect; and (3) NPY may function cooperatively with NE in the PVN to stimulate feeding and drinking beginning at a very early age.

The pharmaco-ontogeny of the perifornical lateral hypothalamic beta 2-adrenergic and dopaminergic receptor systems mediating epinephrine- and dopamine-induced suppression of feeding in the rat.

The functional ontogeny of beta 2-adrenergic and dopaminergic receptors in the perifornical lateral hypothalamus (PLH) that mediate adrenergic and dopaminergic suppression of feeding in rats was investigated. Rat pups, ranging in age from 2 to 15 days, were removed from their mothers and implanted with a brain cannula directed unilaterally at the PLH or a more rostral site lateral to the anterior nucleus of the hypothalamus. On the next day, following a 22-h period of food and water deprivation, each pup was implanted with an intra-oral cannula for oral infusion of milk that could be swallowed or rejected. Subsequently, each pup received an intracerebral injection of saline, or a single dose of epinephrine (EPI, 0.1-30.0 nmol), the beta 2-adrenergic receptor agonist salbutamol (1.0-30.0 nmol) or the dopaminergic receptor agonist apomorphine (1.0-30.0 nmol). Milk intake was then assessed following a 1-h period of infusion. The results showed significant dose-dependent suppression of milk intake in pups as young as 2 days of age in response to PLH injection of EPI, salbutamol and apomorphine. In contrast to its effectiveness in the PLH at 2 days of age, EPI failed to suppress milk intake at this age following injection into a more rostral site lateral to the anterior nucleus of the hypothalamus. Together, these findings suggest that both beta 2-adrenergic and dopaminergic receptors, mediating adrenergic and dopaminergic suppression of feeding, are functionally mature very early in the postnatal development of the rat. Moreover, consistent with evidence in adult rats, these catecholaminergic receptors in young pups appear to be located in the region of the PLH.

The pharmaco-ontogeny of the paraventricular alpha 2-noradrenergic receptor system mediating norepinephrine-induced feeding in the rat.

The present study was undertaken to assess the functional ontogeny of alpha 2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN) that mediate noradrenergic stimulation of feeding in the rat. Rat pups, ranging in age from 2 to 15 days, were removed from their mothers and implanted with a brain cannula directed unilaterally at the PVN or third ventricle. On the following day, each pup was implanted with an intra-oral cannula for oral infusion of milk or water that could be swallowed or rejected. Following a 1-h period of satiation, each pup received an intracerebral injection of saline, or a single dose of norepinephrine (NE, 0.01-100.0 nmol) or the alpha 2-noradrenergic receptor agonist clonidine (0.01-1.0 nmol). Milk or water intake was then assessed following a 1-h period of infusion. Injection of NE into the PVN and third ventricle significantly enhanced milk intake at 2 days of age. NE was 10-fold more potent in the PVN than in the ventricle. While paraventricular injections of NE stimulated milk and water intake equally at 2 days of age, NE produced a greater stimulation of milk than water intake at 15 days of age. Like NE, clonidine significantly enhanced milk intake at 2 days of age following injection into the PVN. Collectively, these findings suggest that alpha 2-noradrenergic receptors, mediating noradrenergic stimulation of feeding, are functionally mature very early in the postnatal development of the rat. Moreover, consistent with evidence in the adult rat, these findings indicate that alpha 2-noradrenergic receptors relevant to feeding are located in the vicinity of the PVN.

The ontogeny of opioid receptors mediating opiate-induced feeding in rats.

Acute administration of naloxone to preweanling rats does not attenuate independent ingestion of milk until 14 days of age suggesting that the full expression of an endogenous opioid system(s), regulating feeding rats, is not complete prior to this age. The present study was undertaken to examine the functional ontogeny of opioid receptors mediating opiate-induced feeding in rats. Rat pups, satiated with milk, were given intraperitoneal injections of the opiate receptor agonist, morphine, and were allowed free access to milk. Morphine stimulated the intake of milk at 3, 5, 7, 14 and 21 days of age, within 2 hr of injection. A time-course analysis in 7-day-old pups showed greater enhancement of intake between hours 2 and 4, than between hours 0 and 2, for large doses of morphine (0.3 and 1.0 mg/kg) suggesting that morphine-induced behavioral depression, which was observed early in the test session, confounded intake at earlier hours. Administration of the opiate receptor antagonist, naltrexone, produced no effect on intake of its own, but blocked the stimulation of intake by morphine in 5-day-old pups confirming that the effect of morphine on the intake of milk was mediated by opioid receptors. Thus, while a functional endogenous opioid system(s), regulating feeding in rats, is not fully mature until 14 days postpartum, the present results suggest that opioid receptors mediating feeding are functional very early in the postnatal development of the rat.

The effects of amphetamine and chlorpromazine on independent ingestion of milk in preweanling rats.

To assess the effects of catecholaminergic drugs on independent feeding during development, preweanling rats were administered amphetamine (AMPH) or chlorpromazine (CPZ) and were allowed to ingest milk through anteriorly located intra-oral cannulas. In 1-hr milk-deprived rat pups, AMPH stimulated milk intake at 3, 7 and 10 days of age and suppressed intake at 15 days. In 22-hr-deprived pups, AMPH had no effect at 3, 7 and 10 days, but reliably suppressed intake at 15 days. CPZ stimulated intake in 3-, 10- and 15-day-old milk-satiated pups. In 22-hr-deprived pups, CPZ had no effect at 3 and 10 days, but stimulated intake at 15 days. While AMPH produced pronounced nonappetitive behavioral activation in conjunction with enhanced intake in 1-hr-deprived pups, AMPH-induced activation occurred without enhanced intake in 22-hr-derived pups. Thus, there was a dissociation between AMPH's effect on milk intake and AMPH-induced nonappetitive behavioral activation. Collectively, the present results support the following conclusions. First, a catecholaminergic system(s) that enhances independent feeding is present very early in postnatal development of the rat. Second, level of food deprivation is an important state-dependent variable when assessing the effects of AMPH and CPZ on independent feeding in preweanling rats.