Effects of D1 and D2 antagonists on apomorphine-induced responses of ventral pallidal neurons.

The ventral pallidum with the adjacent substantia innominata (VP) has been described as a dopaminoceptive brain region. Repeated systemic injections of the dopamine agonist, apomorphine, induce dose-dependent alterations in VP neuronal activity. The present studies evaluated the contribution of D1 and D2 receptor subtypes to apomorphine-induced alterations in extracellularly recorded VP neuronal activity. Both sulpiride (D2 antagonist) and SCH23390 (D1 antagonist) attenuated many of these responses; however, pretreatment with either antagonist did not alter the number of responding neurons, or the maximal effect induced by apomorphine. Thus, activation of either receptor subtype by apomorphine is sufficient to initiate the observed responses, and both may be involved in dopaminergic modulation of VP neurons.

Dopamine D1 and D2 receptor agonists induce opposite changes in the firing rate of ventral pallidal neurons.

Selective dopamine D1 and D2 agonists were used to determine the contributions of each receptor subtype in the modulation of firing rate of ventral pallidum/substantia innominata (VP/SI) neurons. Administration of cumulative doses of the D2 agonist, quinpirole, decreased activity in 59% of the VP/SI cells tested. The decrease in firing rate was dose-dependent between 0.002-0.2 mg/kg i.v. and was blocked by the D2 antagonist, sulpiride (12.5 mg/kg i.v.). In addition, the magnitude and the distribution of responses of VP/SI neurons was not changed following administration of quinpirole as a single versus a divided cumulative dose of 0.1 mg/kg. In contrast, administration of the D1 agonist, SKF38393, excited 69% of the neurons sampled. Similar maximal responses were observed following administration of either a single or a divided cumulative dose of 3.2 mg/kg of SKF38393. The D1 receptor antagonist, SCH23390 (0.1-0.4 mg/kg i.v.) often attenuated the SKF38393-induced increases. The results illustrate that, (1) VP/SI neurons are sensitive to systemically administered dopamine agonists, (2) D1 or D2 receptor activation is sufficient to change the activity of these neurons and (3) these selective agonists mediate opposite effects on VP/SI neuronal activity. These differential responses contrast with effects observed for other dopaminoceptive brain regions, and distinguish VP/SI neurons from morphologically related neurons of the dorsal globus pallidus.

Neuroendocrine evidence for denervation supersensitivity of serotonin receptors: effects of the 5-HT agonist RU 24969 on corticotropin, corticosterone, prolactin and renin secretion.

Serotonergic stimulation can increase the secretion of several hormones through the involvement of different serotonin (5-HT) receptor subtypes. RU 24969, a 5-HT agonist with highest affinity at 5-HT1A and 5-HT1B receptors, increased plasma renin activity (PRA) and plasma renin concentration (PRC) as well as plasma corticosterone and prolactin concentrations in a dose-dependent manner. Inasmuch as 5-HT2 receptors mediate the serotonergic stimulation of renin secretion, we examined the ability of two selective 5-HT2 antagonists, ritanserin and LY53857, to inhibit the neuroendocrine effects of RU 24969. To determine whether the 5-HT receptors which are involved in the stimulation of these hormones are pre- or postsynaptic, RU 24969 was also injected to rats whose brain serotonergic neurons were chemically destroyed by i.c.v. injection of 5,7-dihydroxytryptamine. Both ritanserin and LY53857 blocked the effect of RU 24969 on PRA and PRC, but did not inhibit the RU 24969-induced elevation in plasma corticosterone concentrations. Ritanserin did not inhibit the effect of RU 24969 on prolactin levels, but LY53857 produced a partial inhibition of the RU 24969-induced elevation of prolactin concentrations. In rats with chemical lesions of serotonergic neurons the dose-response curves of RU 24969 for PRA and PRC as well as corticotropin, corticosterone and prolactin shifted to the left, suggesting functional up-regulation of postsynaptic 5-HT receptors.(ABSTRACT TRUNCATED AT 250 WORDS)