Effects of chronic lithium pretreatment on apomorphine-induced penile erection

• 1.1. The effects of chronic lithium pretreatment (600 mg/l in drinking rats, 30 days) on penile erection (PE) induced by apomorphine were investigated in rats. This treatment resulted in a serum Li concentration after 30 days of 0.31 ± 0.01 mmol/l.
• 2.2. Subcutaneous (s.c.) administration of mixed Dl/D2 dopamine receptor agonist apomorphine (0.05–0.5 mg/kg) induced PE in a biphasic manner. The maximum effect was obtained with 0.1 mg/kg of the drug while the response decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg.
• 3.3. Pretreatment of animals with 0.0125-0.1 mg/kg of D1 dopamine receptor antagonist SCH 23390 or D2 dopamine receptor antagonist sulpiride (12.5–100 mg/kg) decreased apomorphine-induced PE. Combination of SCH 23390 (0.025 mg/kg) with sulpiride (12.5 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both D1 and D2 dopamine receptors may be involved in PE induced by apomorphine.
• 4.4. The response induced by apomorphine (0.05-0.5 mg/kg) was decreased in animals pretreated with chronic lithium. The inhibitory effect of sulpiride on apomorphine response, increased in animals pretreated with lithium, in contrast the inhibitory effect of SCH 23390 did not change in this condition. However, a combination of SCH 23390 with sulpiride increased inhibitory effect on apomorphine response in lithium pretreated rats.
• 5.5. It is concluded that chronic lithium inhibits PE induced by dopaminergic mechanism(s).

     

Opposite influences of dopaminergic receptor subtypes on penile erection.

1. Mixed D-1/D-2 dopamine agonist apomorphine induced a penile erection (PE) in rats in a biphasic manner. 2. The response was decreased with increasing doses of the drug. 3. The maximum effect was obtained by 0.1 mg/kg of apomorphine. 4. In animals pretreated with D-1 antagonist SCH 23390, high doses of apomorphine showed higher PE response, while D-2 antagonist sulpiride pretreatment decreased the response of the low doses of the drug. 5. The inhibitory effect of sulpiride was dose-dependent. 6. The D-2 agonists bromocriptine or quinpirole induced a dose-dependent PE. 7. The effects of both drugs were decreased by sulpiride or SKF 38393 pretreatment. 8. Cholinergic drugs physostigmine and neostigmine did not induce PE, but antimuscarinic agent atropine decreased the effects of apomorphine, bromocriptine or quinpirole. 9. It is concluded that D-2 dopamine receptor stimulation may induce PE, while D-1 activation elicit an opposite effect. 10. However, cholinergic stimulation is not able to induce PE, cholinergic inhibition may decrease the PE induced by dopaminergic agents.     

The Effect of Acute Lithium and Rubidium Pretreatment on Apomorphine-Induced Pecking in Pigeons

Abstract: The effects of different doses of lithium (5-320 mg/kg intramuscularly) and rubidium (0.25-32 mg/kg intramuscularly) on apomorphine-induced pecking were investigated in pigeons. These two cations did not induce pecking by itself. Intramuscular administration of apomorphine (a mixed D1/D2 dopamine receptors agonist, 0.1-1.6 mg/kg) induced pecking in a dose-dependent manner. SCH 23390 (Dl dopamine receptor antagonist, 0.02-0.08 mg/kg) and sulpiride (D2 dopamine receptor antagonist, 25-100 mg/kg) decreased apomorphine-induced pecking dose-dependently. Combination of SCH 23390 (0.04 mg/kg) with sulpiride (50 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both Dl and D2 dopamine receptors are involved in apomorphine-induced pecking. The response induced by apomorphine (0.2-0.8 mg/kg) was decreased in animals pretreated with lithium and rubidium. In these conditions, SCH 23390 and sulpiride produced a larger inhibitory effect on the apomorphine response, suggesting that acute lithium and rubidium pretreatment inhibit pecking by interfering with dopaminergic mechanisms.     

Influences of dopamine receptors on chewing behaviour in rats.

1. Intraperitoneal (i.p.) injection of different doses of pilocarpine induced purposeless chewing in rats. Physostigmine (i.p.), but not neostigmine (i.p.) also induced chewing behaviour. 2. Subcutaneous (s.c.) pretreatment of animals with the D-1 receptor blocker SCH 23390 decreased the number of chews induced by pilocarpine. 3. The D-2 dopamine antagonist sulpiride (i.p.) and anticholinergic atropine (i.p.) pretreatment also decreased the frequency of chews induced by the drug. 4. The response induced by pilocarpine (1 mg/kg i.p.) also was dose-dependently decreased in animals pretreated with apomorphine (0.25-1 mg/kg s.c.). 5. Administration of low doses of apomorphine (s.c.) also induced chewing, which was decreased with increasing the doses of the drug. 6. Chewing-induced by apomorphine was decreased by sulpiride or atropine and increased by SCH 23390 pretreatment. 7. Single administration of D-2 dopamine agonist bromocriptine also showed a slight but significant purposeless chewing, which was decreased by sulpiride pretreatment. 8. Single administration of D-2 agonist quinpirole, D-1 agonist SKF 38393 or D-1 antagonist SCH 23390, but not sulpiride caused a slight chewing. 9. It may be concluded that D-1 or D-2 activation exert opposite influences on chewing behaviour in rats, although to prove this effect more elucidation is needed.     

Effects of lithium carbonate on apomorphine-induced sniffing behaviour in rats

Effects of lithium carbonate (Li2CO3) on sniffing induced by apomorphine have been tested in rats. Intraperitoneal administration of different doses of apomorphine (0.25, 0.5 and 1 mg/kg) induced a dose-dependent sniffing response. Chronic Li2CO3 exposure (0.1% in drinking water for 30-35 days) but not acute administration of the drug (320 mg/kg, intraperitoneally) decreased the response of apomorphine. The response to chronic Li2CO3 exposure was observed when apomorphine was injected 60 min., 24 hr or 72 hr after Li2CO3withdrawal, with maximum effect observed when the drug was administered 72 hr after withdrawal of Li2CO3. Blockade of sniffing induced by apomorphine by the D1 dopamine receptor antagonist, SCH23390 (0.005 mg/kg, intraperitoneally) or the D2 dopamine receptor antagonist, sulpiride (25 mg/kg, intraperitoneally) was not increased in acute Li2CO3-treated animals. In animals which were treated chronically with Li2CO3, the blockade of apomorphine response by sulpiride but not by SCH23390 was potentiated. It is concluded that chronic treatment of animals with Li2CO3 is able to alter D2 dopamine receptors response.     

Bromocriptine requires D-1 receptor stimulation for the expression of sniffing behaviour in rats

The effect of the mixed D-1/D-2 dopamine agonist apomorphine, the D-2 agonist bromocriptine and the D- 1-selective dopamine agonist SKF 38393 on sniffing behaviour in rats was tested in the present experiments. Apomorphine induced a dose-dependent sniffing, which was decreased by either D-2 or D-1 dopamine antagonist pre-treatment. Atropine (antimuscarinic drug) or phenoxybenzamine and propranolol (α and β- adrenergic blockers, respectively) did not alter the apomorphine response. Apomorphine induced a significant increase in sniffing in reserpine-treated animals. Bromocriptine produced sniffing during the 3rd hour after drug injection. The effect was decreased by sulpiride or SCH 23390 pre-treatment. Phenoxybenzamine or propranolol did not change the bromocriptine effect, while atropine increased the drug response. SKF 38393 also induced a slight but significant sniffing. In rats pre-treated with reserpine, neither bromocriptine nor the D-1-selective agonist SKF 38393 produced any sniffing. However, the combination of bromocriptine with SKF 38393 produced an intense sniffing behaviour. It may be concluded that bromocriptine requires D-1 receptor stimulation for the expression of sniffing.     

Effect of D-1 or D-2 receptor stimulation on memory retrieval in mice

Mice were trained in one-way active avoidance procedure and retention was tested at 4, 8, 16 and 24 h after training of animals and compared with non-shocked or untrained animals. The effect of drugs was tested on retrieval 24 h after training in other groups of mice. High doses of apomorphine or bromocriptine impaired, while low doses of the drugs improved, retrieval of avoidance. High doses of sulpiride reversed the impairment induced by high doses of these dopamine agonists. Low doses of sulpiride antagonized the improvement of retrieval induced by low doses of apomorphine. SKF 38393 treatment of animals also improved the retrieval. The retrieval impairment induced by higher doses of apomorphine or the improvement induced by different doses of SKF 38393 was antagonized by SCH 23390 pre-treatment. Single administration of SCH 23390 or low doses of sulpiride also impaired retrieval. It is concluded that stimulating post-synaptic D-2 dopamine receptors impairs retrieval whilst activation of pre-synaptic D-2 or post-synaptic D-1 receptors improves memory retrieval.     

Evaluation of dopamine receptor involvement in rat feeding behaviour.

1. The anorectic effect of dopamine agonists and antagonists were studied in rats. 2. Dopamine agonists bromocriptine, quinpirole or SKF 38393 treatment induced, a dose-dependent anorexia in rats. 3. Anorectic effect of bromocriptine was decreased in animals pretreated with pimozide (D-2 antagonist), but not by sulpiride (D-2 antagonist) or SCH 23390 (D-1 antagonist) pretreatment. 4. Anorexia induced by quinpirole was decreased by sulpiride or pimozide, but not by SCH 23390 administration. 5. While sulpiride and SCH 23390 failed to antagonize the anorectic response of SKF 38393, methergoline (5-HT antagonist) decreased anorexia induced by the drug. 6. A combination of quinpirole with SKF 38393 did not elicit potentiated anorectic response. 7. Decrease in food intake induced by bromocriptine, quinpirole or SKF 38393 was potentiated in reserpinized animals, although single administration of reserpine also induced a marked decrease in feeding. 8. Single administration of sulpiride, pimozide or methergoline did not change the feeding behaviour of rats, but SCH 23390 induced anorexia. 9. It is concluded that D-2 activation may induce inhibition of feeding and anorexia induced by SKF 38393 may be mediated through serotonergic mechanism(s).     

Characterization of dopamine receptors involved in apomorphine-induced pecking in pigeons.

1. The possible involvement of subtypes of dopamine-receptors in apomorphine induced pecking was studied in pigeons. Different doses of apomorphine induced pecking in pigeons which was dose-dependent. 2. The response was decreased by SCH 23390 (D-1 antagonist) or high doses of sulpiride (D-2 antagonist) pretreatment, but increased by lower doses of sulpiride. 3. Combination of SCH 23390 with sulpiride completely antagonized the apomorphine effect. 4. Single dose administration of SKF 38393 (D-1 agonist) or bromocriptine (D-2 agonist) and combination of these drugs did not induce pecking, although either SK 23390 or bromocriptine increased the apomorphine-induced pecking which was decreased by SCH 23390 or sulpiride pretreatment. 5. It may be concluded that pecking, induced by apomorphine in pigeons, is elicited through activation of both D-1 and D-2 dopamine-receptors.     

Bromocriptine induces climbing behaviour: possible D-1 or D-2 dopamine receptor involvement

The ability of bromocriptine (BRC), a dopamine D-2 receptor agonist, to induce climbing behaviour was studied in mice. BRC (2–32 mg/kg IP) evoked climbing behaviour. The maximum effect was obtained with 8 mg/kg, while higher doses of BRC (16 and 32 mg/kg) were less effective. Climbing began about 2 h after injection and was most marked 5 h after bromocriptine administration. Pretreatment of animals with the dopamine antagonist pimozide (0.5 mg/kg IP) decreased BRC-induced climbing. Sulpiride (0.25–1.25 mg/kg IP), a potent D-2 antagonist and/or SCH 23390 (0.025 and 0.05 mg/kg SC), a D-1 receptor antagonist, also decreased the response. Furthermore, the climbing behaviour induced by BRC was abolished by pretreatment with reserpine plus alpha-methyl-p-tyrosine (AMPT). Concomitant administration of apomorphine (APO) and BRC potentiated the effect of APO on climbing. Concomitant injection of BRC and SKF 38393 (SKF, D-1 agonist) reduced the effect of SKF on climbing, while administration of BRC 4 h before SKF potentiated the effect of both drugs. It is suggested that BRC induces climbing through D-1 and/or D-2 dopamine receptors.     

Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.

1. The catalepsy induced by dopamine antagonists has been tested and the possible dopamine subtypes involved in catalepsy was determined. 2. Dopamine antagonist fluphenazine, D-1 antagonist SCH 23390 or D-2 antagonist sulpiride induced catalepsy. The effect of fluphenazine and sulpiride was dose-dependent. Combination of SCH 23390 with sulpiride did not induce catalepsy potentiation. 3. D-1 agonist SKF 38393 or D-2 agonist quinpirole decreased the catalepsy induced by fluphenazine, SCH 23390 or sulpiride. 4. Combination of SKF 38393 with quinpirole did not cause potentiated inhibitory effect on catalepsy induced by dopamine antagonists. 5. The data may indicate that although D-2 receptor blockade is involved in catalepsy, the D-1 receptor may plan a role.     

Differential effects of dopamine agonists on locomotion in intact and reserpine-treated mice.

1. Apomorphine and bromocriptine induced a dose-dependent locomotion in mice. The responses of both drugs were decreased by SCH 23390 or sulpiride pretreatment. 2. Locomotor activity induced by apomorphine was increased and that of bromocriptine was decreased by reserpine. 3. SKF 38393 or quinpirole also induced locomotion. The response of SKF 38393 was decreased by reserpine. 4. Combination of SKF 38393 with bromocriptine induced a significant locomotor activity different from that of SKF 38393 or bromocriptine in reserpinized animals. 5. Combination of quinpirole with bromocriptine even decreased the response of bromocriptine in intact animals. 6. In conclusion, bromocriptine needs intact dopaminergic neurons and activation of D-1 receptor for expression of locomotion. High doses of quinpirole may induce locomotor activity possibly through D-1/D-2 receptor activation and quinpirole may potentiate the effect of bromocriptine on autoreceptor for inducing sedation.     

Effect of the dopamine D-1 antagonist SCH 23390 on rotational behaviour induced by apomorphine and pergolide in 6-hydroxy-dopamine denervated rats

The experiments concerned the effects of the D-1 dopamine antagonist SCH 23390 on the rotational behaviour induced by apomorphine and pergolide in 6-hydroxy-dopamine denervated rats. SCH 23390 dose dependently inhibited the rotational behaviour induced by apomorphine. A significant inhibitory effect was obtained after 0.05 mg/kg s.c. of SCH 23390, which involved a change of the typical two-peak pattern of rotation induced by apomorphine. While the first peak of rotation was not significantly modified, the last peak of rotation induced by apomorphine was inhibited in a dose-dependent manner. No significant inhibition of the total rotation induced by pergolide was observed after SCH 23390 pretreatment. SCH 23390 seemed to enhance the duration of the rotation induced by pergolide, resulting in an increase in the total number of turns. However, the intensity of the maximal peak of rotation induced by pergolide was significantly inhibited after 5.0 mg/kg s.c. of SCH 23390. Comparison of the potency with which SCH 23390 inhibited the apomorphine- and pergolide-induced maximal peaks of rotation reveals that SCH 23390 was approximately 100 times more potent in inhibiting the apomorphine than the pergolide response. The results, compared with those in our previous report, show that the D-2 dopamine antagonist sulpiride was 1000 times more potent in inhibiting the pergolide than the apomorphine rotation. The present results support the hypothesis that apomorphine and pergolide induce rotation in 6-hydroxy-dopamine denervated rats by differential actions on D-1 and D-2 receptor sites.     

Involvement of dopamine receptor subtypes in mouse thermoregulation

The effects of dopamine agonists on core body temperature (BT) were tested in mice. Apomorphine (APO) reduced BT of the mice dose dependently. The response was inhibited by the D-2 antagonist sulpiride, but not by the D-1 antagonist SCH 23390. The D-2 agonist quinpirole also decreased BT and this was prevented by sulpiride pretreatment. Administration of the D-1 agonist SKF 38393 increased BT. This hyperthermia was decreased by SCH 23390 pretreatment. In reserpinized animals, APO caused a dose-related increase in BT. The hyperthermic response of the drug was abolished in animals pretreated with a combination of sulpiride with SCH 23390, but not by single administration of sulpiride or SCH 23390. Quinpirole and SKF 38393 caused hyperthermia in reserpinized mice. The response was decreased in animals pretreated with sulpiride or SCH 23390, respectively. BT of the intact mice was decreased, while that of reserpinized animals was increased by SCH 23390 but not by sulpiride pretreatment. It is concluded that the presynaptic dopamine neurons are involved in hypothermia, while both post-synaptic D-1 and D-2 dopamine receptors may mediated the hyperthermia induced by dopaminergic agents.     

Synergistic effects between D-1 and D-2 dopamine antagonists on catalepsy in rats

The effect of selective D-1 and D-2 dopamine agonists on catalepsy induced by various dopamine antagonists was studied. A potent and selective D-2 antagonist, YM-09151 (YM-09151-2) at a dose of 1.2 mg/kg, SC and a selective D-1 antagonist, SCH 23390 at 1.0 mg/kg, SC induced catalepsy in rats. Mixed D-1/D-2 antagonists, haloperidol (HPD) and cis-flupentixol (FLU) also induced catalepsy at doses of 2.0 and 0.8 mg/kg, SC, respectively. A mixed D-1/D-2 agonist, apomorphine (1.0 mg/kg, SC), a selective D-2 agonist, bromocriptine (10 mg/kg, IP) and a muscarinic antagonist, scopolamine (1.0 mg/kg, SC), prevented or markedly reduced the incidence of catalepsy by the tested antagonists. In contrast, a selective D-1 agonist, SKF 38393 (4.0 mg/kg, SC) did not reduce the cataleptogenic effects of HPD, FLU and SCH 23390, but did reduce the effect of YM-09151. Moreover, co-administration of YM-09151 with SCH 23390 produced a marked increase in the incidence of catalepsy. The incidence seen after the combination of YM-09151 and SCH 23390 at low doses was significantly different from that seen after each drug alone at the doubled dose. Thus, D-1 and D-2 antagonists potentiated each other's effect in producing catalepsy. These results suggest an important role of both D-1 and D-2 receptors in the catalepsy and the existence of synergistic effects of D-1 and D-2 receptor blockade.     

The mode of action of bromocriptine following pretreatment with reserpine and α-methyl-p-tyrosine in rats

The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and -methyl-p-tyrosine (-MPT). BRC (1–20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5–20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), -MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus -MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC), a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy. Furthermore, haloperidol (0.02 and 1.0 mg/kg IP), sulpiride (20 mg/kg IP) or scopolamine (0.5 mg/kg IP) inhibited BRC-induced yawning, but prazosin (1.0 and 3.0 mg/kg IP), an -1 receptor antagonist, did not affect this behavior. These results suggest that BRC-induced yawning may be mediated via presynaptic dopaminergic neuron activity and that BRC, in addition to the stimulation of dopamine D-2 receptors, appears to require endogenous dopamine or receptor activation by another dopamine agonist (D-1 agonist) for the induction of yawning, stereotypy and upright fighting responses. The ability of dopamine agonists to induce these behaviors seems to depend apon the potency and ratio of D-2 versus D-1 receptor activity.     

Effect of dopamine D-1 and D-2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo

Summary The effect of the dopamine (DA) D-1 agonist SKF 38393, the D-2 agonist LY 171555 and the mixed D-1/D-2 agonist apomorphine on striatal DA release and metabolism was tested in vivo using an intracerebral dialysis method in halothane-anaesthetized rats. The specificity of responses to these agonists was tested using the selective DA antagonists SCH 23390 (D-1) and sulpiride (D-2).Both LY 171555, 0.01 mg/kg, and SKF 38393, 10 mg/kg, reduced levels of DA in striatal perfusates. Neither SCH 23390, 0.5 and 5 mg/kg, nor sulpiride, 10 mg/kg, affected levels of DA in striatal perfusates, but 250 mg/kg sulpiride caused a DA increase. The decrease of DA levels induced by LY 171555 (0.01 mg/kg) was prevented by pretreatment with sulpiride (10 mg/kg) but not SCH 23390 (0.5 mg/kg). In comparison, pretreatment with SCH 23390 (0.5 mg/kg) completely inhibited the reduction of DA induced by SKF 38393 (10 mg/kg) while sulpiride (10 mg/kg) was without effect. Apomorphine (0.05 mg/kg) also decreased DA in striatal perfusates and this action was partially inhibited by both SCH 23390 (0.5 mg/kg) and sulpiride (10 mg/kg).Levels of the DA metabolite DOPAC in striatal perfusates also significantly decreased following LY 171555 (0.01 mg/kg) and apomorphine (0.05 mg/kg) but not SKF 38393 (10 mg/kg). The antagonist SCH 23390, in a dose, 0.5 mg/kg, that alone did not increase levels of DOPAC, inhibited the reduction of DOPAC induced by both LY 171555 and apomorphine. Sulpiride, 10 mg/kg, caused a marked increase in striatal DOPAC and this was not affected by a subsequent injection of LY 171555, SKF 38393 or apomorphine.We conclude from these data that DA release in rat striatum is autoregulated by independent D-1 and D-2 receptor-linked mechanisms. In contrast, the level of DA metabolism is controlled by a D-2 receptor-coupled mechanism which can be influenced by the D-1 receptor. This study provides further evidence that DA release and DA synthesis/metabolism are able to change independent of each other.     

The dopaminergic system plays a role in the effect of lithium on inhibitory avoidance memory in mice

The effects of dopaminergic drugs on the inhibitory avoidance memory affected by lithium were examined in the Naval Medical Research Institute (NMRI) mice using a single-trial step-down inhibitory (passive) avoidance task. The results showed that post-training administration of lithium (10 mg/kg, i.p.) decreased the step-down latency on the test day, which was fully or partly reversed by pre-test administration of the same dose of the drug; suggesting state-dependent learning induced by lithium. Our results also showed that pre-test (i.p.) administration of the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole by themselves and in combination with ineffective doses of lithium (0.3, 0.6 and 1.25 mg/kg) reversed the decrease of the step-down latency induced by post-training lithium. In contrast, pre-test administration of the dopamine D1 receptor antagonist SCH23390 (0.025, 0.05 and 0.1 mg/kg, i.p.) and the dopamine D2 receptor antagonist sulpiride (6.25 and 12.5 mg/kg, i.p.) alone or in combination with pre-test lithium (10 mg/kg), did not significantly alter the step-down latency on the test day, except for a higher dose of sulpiride (25 mg/kg) which by itself increased the step-down latency. Furthermore, pre-test administration of a lower dose of sulpiride (3 mg/kg) in combination with ineffective doses of lithium (03, 0.6 and 1.25 mg/kg) also reversed the decrease in the step-down latency induced by post-training lithium. In conclusion, the dopamine D1 and D2 receptor mechanism(s) may be involved, at least partly, in the effect of lithium on retrieval of the inhibitory avoidance memory influenced by the drug.     

Behavioural effects of selective dopamine D-1 and D-2 agonists and antagonists in guinea-pigs

This study describes specific behaviours in guinea-pigs after dopamine D-1 and D-2 receptor activation which differed to those described in other rodent species. Intraperitoneal (IP) administration of the dopamine D-2 receptor agonist quinpirole (1.5, 3 and 6 mg/kg) to guinea-pigs dose-dependently initiated locomotor activity and other behaviours including rearing, head-down sniffing, chewing, circling, licking and head/body shaking. Locomotor activity induced by quinpirole (3 mg/kg) was reduced by the D-2 receptor antagonists sulpiride, (100 mg/kg IP) and raclopride (10 mg/kg IP). The dopamine D-1 receptor agonist SKF 38393 (8, 16 and 32 mg/kg IP) produced little or no behavioural effect, nor did the D-1 receptor antagonist SCH 23390 (0.2 and 0.4 mg/kg IP). A 16 mg/kg dose of SKF 38393, given in combination with 3 mg/kg quinpirole, produced responses similar to quinpirole alone, whereas 32 mg/kg SKF 38393 combined with quinpirole induced vacuous oral chewing, with attenuation of locomotor activity and circling, but not other behaviours produced by this dose of quinpirole. In contrast to previous studies in rats, the responses to quinpirole (3 mg/kg) were not significantly affected by SCH 23390 (0.2 and 0.4 mg/kg). It is concluded that the guinea-pig may be a useful and interesting species for study of the behavioural effects of D-1 and D-2 agonists and antagonists, as its responses appear to differ from those of other rodent species, but are similar to some responses to D-1 agonists observed in primates.     

Repeated administrations of dopamine receptor agents affect lithium-induced state-dependent learning in mice

The influence of repeated administration of dopamine receptor agents on the effect of lithium on lithium-induced state-dependent learning was examined in mice. Immediate post-training intraperitoneal (i.p.) administrations of lithium (10 and 20 m/kg) decreased the step-down latency of a single-trial inhibitory avoidance task. This was fully or partly reversed by pre-test administration of the same doses of the drug, with maximum response at the dose of 10 mg/kg, suggesting state-dependent learning was induced by lithium. Here, it has also been shown that repeated intracerebroventricular administrations of a mixed D1/D2 dopamine receptors agonist apomorphine (once daily injections of 0.5 microg/mouse for three consecutive days followed by five days of no drug treatment) increased the effect of lower doses of pre-test lithium (1.25, 2.5 and 5 mg/kg, i.p.) on the reinstatement of the step-down latency decreased by post-training lithium (10 mg/kg). On the contrary, not only repeated administrations of the dopamine D1 receptor antagonist SCH 23390 (0.5 and 1 microg/mouse) but also the dopamine D2 receptor antagonist sulpiride (0.3 and 1 microg/mouse) disrupted the state-dependent learning induced by lithium. These results suggest that state-dependent learning induced by lithium may be altered by repeated pretreatment of dopamine receptor agents.