ergoline and clebopride

A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Acetylcholine; Animals; Benzamides; Benzazepines; Corpus Striatum; Dopamine Agonists; Ergolines; Humans; Infant, Newborn; Male; Oxidopamine; Quinpirole; Rats; Rats, Sprague-Dawley; Time Factors

The D1- and D2-mediation of stimulated motor behavior was studied in pups (Days 10-11) and weanlings (Days 20-21) that had been depleted of dopamine (DA) on postnatal Day 3. Administration of the D1-like agonist SKF 38393 (30.0 mg/kg) or the D2-like agonist quinpirole (3.0 mg/kg) increased the incidence of sniffing and locomotion in intact and DA-depleted animals tested at either age. However, the ability of selective DA antagonists to reduce these stimulated responses interacted with both the depletion and the age at the time of testing. When tested as pups, both the D1 antagonist SCH 23390 (0.2 or 0.4 mg/kg) and the D2 antagonist clebopride (10.0 mg/kg) suppressed the behaviors induced by either class of DA agonist. When tested as weanlings, intact animals exhibited the profile of pups (i.e., either antagonist blocked each agonist). In DA-depleted weanlings, however, only the D1 antagonist blocked the D1 agonist-induced responses and only the D2 antagonist blocked the D2 agonist-induced responses. These data demonstrate that the interactions between D1 and D2 receptors in the expression of stimulated motor behaviors are altered following DA depletions in neonates. Moreover, this change in receptor function occurs sometime between 7 and 13 days after the DA depletion.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Aging; Animals; Animals, Newborn; Benzamides; Benzazepines; Brain; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Ergolines; Female; Male; Motor Activity; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Stereotyped Behavior

Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Apomorphine; Benzamides; Benzazepines; Body Temperature; Dose-Response Relationship, Drug; Ergolines; Female; Mice; Quinpirole; Receptors, Dopamine; Stereotyped Behavior

The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Apomorphine; Benzamides; Benzazepines; Clopenthixol; Dopamine; Dose-Response Relationship, Drug; Ergolines; Flupenthixol; Hydroxydopamines; Hypothalamus; Male; Motor Activity; Oxidopamine; Pergolide; Rats; Rats, Inbred Strains; Receptors, Dopamine; Spiperone

The selective dopamine (DA) D-1 antagonist SCH 23390 antagonized the contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 in rats lesioned unilaterally with 6-hydroxy-DA but had a 600 times weaker effect against the preferential DA D-2 agonist pergolide. The D-2 antagonists clebopride and spiroperidol had the reverse selectivity. The mixed D-1/D-2 antagonists cis(Z)-flupentixol and cis(Z)-clopenthixol blocked the circling induced by either agonist. It is concluded that circling behaviour is mediated by closely related but independent DA D-1 and D-2 receptor sites.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amphetamine; Animals; Antipsychotic Agents; Appetite Depressants; Benzamides; Benzazepines; Catalepsy; Clopenthixol; Ergolines; Flupenthixol; Humans; Hydroxydopamines; Male; Oxidopamine; Pergolide; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Stereotyped Behavior