The effects of dopaminergic drugs in the ventral hippocampus of rats in the nicotine-induced anxiogenic-like response

Nicotine an active alkaloid of tobacco has dopaminergic properties. The drug alters anxiety-like behavior in rodents. Ventral hippocampus (VHC) may be a site for modulation of anxiety-like behaviors. The possible involvement of ventral hippocampal dopaminergic receptor mechanism in the nicotine influence on anxiogenic-like response has been investigated in the present study. The effects of apomorphine, sulpiride and SCH23390 on nicotine response in elevated plus maze in rats have been investigated. Intraperitoneal administration of nicotine (0.6 mg/kg) decreased percentage of open arm time (%OAT) but not percentage of open arm entries (%OAE) and locomotor activity, indicating an anxiogenic-like response. Intra-hippocampal injection (intra-VHC) of apomorphine, a D₁/D₂ dopamine receptor agonist (0.1 and 0.2 μg/rat) also caused anxiogenic-like effects, but the drug blocked that of nicotine. Intra-VHC administration of the D₂ receptor antagonist, sulpiride (1, 2.5 and 5 μg/rat) or the D₁ receptor antagonist, SCH23390 (0.01, 0.1 and 1 μg/rat) did not elicit any response. However, pretreatment with sulpiride (1 μg/rat) or SCH23390 (0.1 μg/rat) decreased nicotine's effect. The results may indicate a modulatory effect for the D₁ and D₂ dopamine receptors of VHC in the anxiogenic-like response induced by nicotine.     

Dopaminergic modulation of transcallosal activity of cat motor cortical neurons

The effects of dopamine (DA) and its antagonists on the transcallosal activity of pyramidal tract neurons (PTNs) and non-PTNs in the anesthetized cat motor cortex were studied with iontophoretic applications; dopamine, SCH 23390 (D1 antagonist), sulpiride (D2 antagonist) and haloperidol. Neuronal activity was recorded with a multi-barreled glass microelectrode. Transcallosal neuronal activity was evoked by stimulation of the contralateral motor cortex. The number of spikes thus activated was counted for the control and test conditions after application of each drug: (1) dopamine application decreased the number of spikes evoked by transcallosal stimulation; (2) application of SCH 23390, sulpiride and haloperidol restored these decreased spike numbers to the control level; (3) latency of neuronal response to transcallosal stimulation was not affected by the application of either DA, SCH 23390, sulpiride or haloperidol; and (4) there was no significant difference between PTNs and non-PTNs in the manner of response to DA and its antagonist applications. Our conclusion is that dopamine modulated the transcallosal neuronal response in the cat motor cortex in a suppressive manner. This fact suggested that interhemispheric neuronal communications could be subjected to suppressive modification by the dopaminergic system.     

A 68930 and dihydrexidine inhibit locomotor activity and d-amphetamine-induced hyperactivity in rats: a role of inhibitory dopamine D(1/5) receptors in the prefrontal cortex?

The behavioral and biochemical effects of the full dopamine D(1/5) receptor agonists, dihydrexidine and (1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCl (A 68930), were examined in rats. Both A 68930 (0-4.6 mg kg(-1), s.c.) and dihydrexidine (0-8.0 mg kg(-1), s.c.) caused a dose-dependent suppression of locomotor activity, as assessed in an open-field. This locomotor suppression was dose-dependently antagonized by the selective dopamine D(1/5) receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (SCH 23390; 0-5.0 microg kg(-1), s.c.), but not by the selective dopamine D(2/3) receptor antagonist raclopride (0-25.0 microg kg(-1), s.c.). Furthermore, A 68930 and dihydrexidine did not cause any locomotor activity in habituated rats that displayed a very low base-line activity. Neither did A 68930 nor dihydrexidine produce any excessive stereotypies that could possibly interfere with and mask ambulatory activity. In fact, both A 68930 and dihydrexidine potently blocked hyperactivity produced by d-amphetamine (0-4.0 mg kg(-1), s.c.). Such findings traditionally would be interpreted as a sign of potential antipsychotic properties of A 68930 and dihydrexidine. Examination of neuronal activation, as indexed by the immediate early gene c-fos, showed that A 68930 and dihydrexidine caused a highly significant expression of c-fos in the medial prefrontal cortex. This c-fos expression was sensitive to treatment with SCH 23390, but not with raclopride. The effects of A 68930 and dihydrexidine on c-fos expression in caudate putamen or nucleus accumbens were less marked, or undetectable. The results indicate that stimulation of dopamine D(1/5) receptors, possibly in the medial prefrontal cortex, is associated with inhibitory actions on locomotor activity and d-amphetamine-induced hyperactivity. Assuming an important role of prefrontal dopamine D(1/5) receptors in schizophrenia, such inhibitory actions of dopamine D(1/5) receptor stimulation on psychomotor activation may have interesting clinical implications in the treatment of schizophrenia.     

Effects of estrogen and progesterone on the expression of connexin-36 mRNA in the suprachiasmatic nucleus of female rats

In rat, helium pressures induce locomotor and motor activity which requires dopaminergic and N-methyl-D-aspartate (NMDA) receptor activities at striatal level. However, biochemical studies have suggested that pressure exposure may increase striatal glutamate level. We used microdialysis technique to study the effects of pressure on glutamate level in the striatum and the effects of local administration of D1 (SCH23390) or D2 (sulpiride) on these changes. Pressures increase both glutamate and glutamine levels in striatal microdialysates. Administration of sulpiride (1 microM) or SCH23390 (1 microM) by reverse microdialysis did not affect significantly pressure induced glutamate increase. So, protective effects of D1 and D2 antagonists against locomotor and motor hyperactivity (LMA) are probably independent of the processes involved in the striatal glutamate increase evoked by pressure.     

Effect of dopamine blockers on cerebral ischemia-induced hyperactivity in gerbils.

When common carotid arteries of Mongolian gerbils were clamped for 5 min, locomotor activity significantly increased the day after the ischemic insult. This hyperactivity induced by cerebral ischemia was evident in both light and dark periods. The significant increases in locomotor activity seen in both periods were noted for 3 and 9 days after occlusion, respectively. Effects of dopamine receptor antagonists on the ischemia-induced hyperactivity were investigated the day after the ischemia insult. Haloperidol, sulpiride, and eticlopride, all dopamine D2 receptor antagonists, decreased the ischemia-induced hyperactivity at doses that had no effects on locomotor activity in sham-operated animals. SCH23390, a dopamine D1 receptor antagonist, had no clear effects on the ischemia-induced hyperactivity. Clozapine, with not so high an affinity for the dopamine D2 receptor decreased the ischemia-induced hyperactivity when given in a relatively high dose. Thus, the ischemia-induced hyperactivity is apparently related to abnormalities in dopaminergic functions, particularly the dopamine D2 receptor.     

Presynaptic autoinhibition of the electrically evoked dopamine release studied in the rat olfactory tubercle by in vivo electrochemistry.

Evoked dopamine release was monitored in vivo from the olfactory tubercle of anaesthetized rats by differential pulse amperometry combined with carbon fibre electrodes which, in most cases, were electrochemically treated. Dopamine release was evoked by electrical stimulation of the ascending dopaminergic pathway. The dopamine release evoked by burst stimulation (20 s with a mean frequency of 6 Hz) was dose-dependently decreased by D,L-apomorphine (25-800 micrograms/kg, s.c.) or by quinpirole (50 micrograms/kg, s.c.) while the opposite effect was observed with haloperidol (12.5 micrograms/kg-0.5 mg/kg, s.c.) or with D,L-sulpiride (2-200 mg/kg, s.c.). Neither the D1 agonist SKF 38393 (10 mg/kg, s.c.) nor the D1 antagonist SCH 23390 (0.5 mg/kg, s.c.) affected the evoked dopamine release. Moreover, sulpiride competitively antagonized the effects of apomorphine. The relative amplitude of the apomorphine inhibition was inversely correlated with the stimulation frequency (6 or 9 Hz). The increase induced either by haloperidol or by sulpiride was positively related to the stimulation frequency (from 3 to 9 Hz) and reached a stable value (+700% of the pre-drug-evoked dopamine release) with higher frequencies (from 9 to 20 Hz). This increase also depended on the duration of the stimulation: both single-train (10 pulses) or burst stimulations for 20 s, whose frequency inside the trains was in both cases 14 Hz, evoked a dopamine release which was minimally affected by sulpiride or haloperidol. In conclusion, in physiological conditions the amplitude of the impulse flow-dependent dopamine release is regulated by the extrasynaptic extracellular dopamine concentration which varies from 10 to 100 nM. This presynaptic autoinhibition is mediated by autoreceptors of the D2 type and is involved in the nonlinear relationship between impulse flow and dopamine release.     

Effects of SCH 23390 and sulpiride on the reinforced responding of the young rat.

Reinforced responding of 17-day-old rat pups was assessed after blockade of dopamine D1 and D2 receptor systems. Rat pups were trained to traverse a straight alley for nipple attachment reward and then injected with various doses of either sulpiride (D2 antagonist), SCH 23390 (D1 antagonist), or a combination of sulpiride and SCH 23390. The approach performance of drug-treated pups was then compared with vehicle-treated pups on both reinforcement and extinction trials. SCH 23390, but not sulpiride, depressed the appetitive approach responding of the pups. During extinction testing, SCH 23390-treated pups had longer response latencies than pups given vehicle. "Best score" data suggested that SCH 23390 primarily affected reward processes and not motor capability. Most important, the effects of SCH 23390 on reinforced responding were potentiated by sulpiride, suggesting that both the D1 and D2 receptor systems are involved in reward processes.     

The effects of dopamine and its antagonists on directional delay-period activity of prefrontal neurons in monkeys during an oculomotor delayed-response task

To examine the role of dopamine receptors in the memory field of neurons for visuospatial working memory in the prefrontal cortex (PFC), dopamine and its antagonists (SCH23390 for the D1-antagonist and sulpiride for the D2-antagonist) were applied iontophoretically to neurons of the dorsolateral PFC in monkeys that performed an oculomotor delayed-response task. In this task, the subject made a memory-guided saccade to a remembered target location that had been cued by a visuospatial stimulus (right, up, left, or down; 15 degrees in eccentricity) prior to a 4-s delay period. We focused here on PFC neurons that showed directional delay-period activity; i.e., an increased activity during the delay period, the magnitude of which varied significantly with the target location. Iontophoretic application of SCH23390 (usually 50 nA) decreased or increased the activities of most of these neurons (n=48/62, 77%); most neurons showed a decrease (n=43/62, 69%). For the neurons affected by SCH23390, a directional index of directional delay-period activity was attenuated by SCH23390, whereas the preferred direction was not greatly affected. The decreasing effect of SCH23390 was dose-dependent; the extent of the decrease was less with a lower dose (20-nA current) than with the ordinary dose (50-nA current), although the effect of the lower dose of SCH23390 on delay-period activity was similar in nature to that of the ordinary dose of SCH23390. Furthermore, the application of dopamine itself augmented directional delay-period activity in most of the neurons tested (n=12/16, 75%). Sulpiride did not have any significant effects in most of the neurons tested (n=15/17). These results suggest that the activation of D1-dopamine receptors play a facilitating role in the memory field of PFC neurons for visuospatial working memory processes.     

Effect of D1 receptor stimulation in normal and MPTP monkeys

The effect of a selective agonist of the dopamine D1 receptor (SKF 38393) and of the D2 receptor (LY-171555) was tested acutely in normal and in monkeys with a parkinsonian syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The D2 agonist induced a strong locomotor response and lingual dyskinesia in both normal and parkinsonian monkeys. The D1 agonist however had no locomotor effect by itself but induced tongue protrusions in normal monkeys only. It appeared to potentiate the dyskinetic effect of LY 171555 in MPTP monkeys but it antagonized the locomotor action of the D2 agonist in both normal and MPTP monkeys. The selective D1 and D2 antagonists SCH 23390 and sulpiride were also tested. Both compounds were able to suppress the dyskinetic action of the combined agonists in normal animals but only the D2 antagonist was effective in the same conditions in MPTP monkeys. These findings emphasize the importance of the D2 receptor in mediating the locomotor response as well as dyskinesia in monkeys.     

Dual effects of L-3,4-dihydroxyphenylalanine on aromatic L-amino acid decarboxylase, dopamine release and motor stimulation in the reserpine-treated rat: evidence that behaviour is dopamine independent

The comparative effects of L-3,4-dihydroxphenylalanine (L-DOPA) on dopamine synthesis, release and behaviour were studied in the reserpine-treated rat. Acute administration of L-DOPA (25-200 mg/kg) dose-dependently inhibited the activity of aromatic L-amino acid decarboxylase (AADC) in the substantia nigra and corpus striatum. The antiparkinsonian drugs budipine (10 mg/kg) and amantadine (40 mg/kg) enhanced AADC activity in these regions, and prevented or reversed AADC inhibition by L-DOPA. Dual probe dialysis revealed that low doses of L-DOPA (25-50 mg/kg) dose-dependently stimulated the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in nigra and striatum, whilst high doses of L-DOPA (100-200 mg/kg) completely suppressed the release of dopamine, but not DOPAC. Sulpiride (50 microM) administered via the probes antagonized dopamine release in response to 25 mg/kg L-DOPA, but greatly facilitated release by 200 mg/kg L-DOPA. Dopamine release was blocked by the centrally acting AADC inhibitor NSD 1015, but facilitated by the central AADC activator budipine. In behavioural tests L-DOPA (plus benserazide, 50 mg/kg) only reversed akinesia at 200 mg/kg, and not at 25-100 mg/kg. Pretreatment with either NSD 1015 (100 mg/kg) or budipine (10 mg/kg) markedly potentiated the motor stimulant action of a threshold dose of L-DOPA (100 mg/kg). A combination of NSD 1015 (100 mg/kg) and benserazide (50 mg/kg) potentiated L-DOPA behaviour more effectively than either inhibitor alone. NSD 1015-facilitated L-DOPA behaviour was antagonized by sulpiride (100 mg/kg) and not by SCH 23390 (1 mg/kg), whereas budipine-facilitated L-DOPA behaviour was fully antagonized by SCH 23390 and only partially by sulpiride. These results show that behaviourally active doses of L-DOPA in the reserpinized rat are not accompanied by significant increases in extracellular dopamine and are therefore probably not dopamine mediated. We propose that L-DOPA is capable of directly stimulating dopamine D2 and possibly non-dopamine receptors, thereby inhibiting dopamine efflux presynaptically and promoting motor activation postsynaptically. A stimulant action of L-DOPA on motor behaviour, preferentially mediated by D1 > D2 receptors, suggests that L-DOPA may also be capable of yielding a dopamine-like response in the absence of detectable dopamine release. These findings are incorporated into a new model of L-DOPA's actions in the reserpinized rat, and their possible implications for our understanding of L-DOPA in Parkinson's disease are discussed.     

Locomotor activity and accumbens Fos expression driven by ventral hippocampal stimulation require D1 and D2 receptors

Numerous studies have suggested that excitatory projections from the ventral hippocampus to the nucleus accumbens modulate locomotor activity in rats. Furthermore, the ability of ventral hippocampal neurons to alter locomotor activity may involve the dense dopaminergic innervation found in the nucleus accumbens. The purpose of this study was to: (i) more fully characterize the locomotor effects of acute alterations in ventral hippocampal activity; (ii) ascertain the influence of dopamine agonists and antagonists on locomotor changes produced by altered ventral hippocampal activity; and (iii) use immediate early gene induction to determine whether dopamine antagonists alter the response of nucleus accumbens neurons to ventral hippocampal stimulation. By comparing a variety of excitatory amino acid agonists, it was found that ventral hippocampal infusion of N-methyl-D-aspartate elevated locomotor activity in a subconvulsive manner, while other excitatory amino acid receptor agonists did not. Inactivation of the ventral hippocampus achieved by lidocaine infusion did not suppress ongoing locomotor activity, nor did it affect amphetamine-induced increases in locomotor activity. Increases in locomotor activity induced by ventral hippocampal N-methyl-D-aspartate infusion were blocked by systemic administration of haloperidol (a D2 receptor antagonist), SCH-23390 (a D1 receptor antagonist) or reserpine. Cellular expression of the protein product of the immediate early gene, c-fos, was dramatically increased in the nucleus accumbens shell after ventral hippocampal N-methyl-D-aspartate infusion, and haloperidol, SCH-23390 and reserpine attenuated this effect. These results suggest that the increases, but not decreases, in ventral hippocampal activity have a measurable effect on ongoing rates of locomotion, and that this effect requires both D1 and D2 receptors. Moreover, the studies of Fos expression suggest that dopamine receptor antagonists attenuate neuronal responses to ventral hippocampal stimulation within the nucleus accumbens, a brain region important in the generation and maintenance of locomotor activity.     

Morris water maze learning in Long-Evans rats is differentially affected by blockade of D1-like and D2-like dopamine receptors

Dopaminergic neurotransmission is involved in several brain functions including spatial cognition. In the present study we examine the effects of systemic administration of D1-like receptor antagonist SCH23390 and D2-like receptor antagonist sulpiride on the acquisition of the Morris water maze task. We used visible versus hidden platform versions of the MWM in order to distinguish between the effects of the drugs on the procedural versus cognitive aspects of the task. SCH23390 was found to prolong escape latencies to the visible platform at a higher dose (0.05mg/kg), whilst the lower dose (0.02mg/kg) left both procedural and cognitive functions almost unchanged. SCH23390 was also found to reduce swimming speed. Sulpiride did not affect the visible platform learning at any of three doses studied (30, 60 and 100mg/kg); the highest dose of sulpiride (100mg/kg) impaired place navigation to the hidden platform, without affecting the swim speed. The results of the present study show a difference in the involvement of D1-like and D2-like receptors in the MWM acquisition.     

Repeated administration of SCH 23390 enhances the SKF 38393-induced inhibition in the rat hippocampus

The functional modification of the D1 dopamine receptor subtype following acute or repeated administration of the D1 receptor antagonist SCH 23390 (0.5 mg/kg s.c.) was studied in the rat hippocampal slice preparation. The activity of the D1 receptor system was evaluated by measuring the effect of the D1 receptor agonist SKF 38393 on the spontaneous firing of CA1 hippocampal neurons. The testing was performed 1, 2 and 7 days after discontinuation of the treatment. Repeated (21 days, once daily), but not acute, administration of SCH 23390 significantly potentiated the inhibitory reaction to SKF 38393. The inhibition evoked by SKF 38393 was blocked by application of SCH 23390 (10(-8) M). The results show that repeated treatment with SCH 23390 enhances the inhibitory effect of SKF 38393 in the rat hippocampus, probably due to an increase in the number of D1 dopamine receptors.     

Role of accumbens and cortical dopamine receptors in the regulation of cortical acetylcholine release.

Cortical acetylcholine, under resting and stimulated conditions, was measured in frontoparietal and prefrontal cortex using in vivo microdialysis in freely-moving rats. Cortical acetylcholine efflux was stimulated by systemic administration of the benzodiazepine receptor partial inverse agonist FG 7142. Administration of FG 7142 (8.0 mg/kg; i.p.) significantly elevated acetylcholine efflux in both cortical regions (150-250% relative to baseline) for 30 min after drug administration. The ability of endogenous dopamine to regulate cortical acetylcholine efflux under resting or stimulated conditions and the relative contributions of D1- and D2-like dopamine receptor activation was also assessed. In a first series of experiments, systemic administration of the antipsychotic drug haloperidol (0.15, 0.9 mg/kg, i.p.) blocked FG 7142-stimulated acetylcholine efflux in frontoparietal, cortex while the D1-like antagonist, SCH 23390 (0.1, 0.3 mg/kg), was less effective in attenuating stimulated acetylcholine efflux. In a second series of experiments, the effects of infusions of these antagonists and of the D2-like antagonist sulpiride (10, 100 microM) into the nucleus accumbens were assessed. Infusions of haloperidol and sulpiride significantly blocked FG 7142-stimulated acetylcholine efflux while SCH 23390 did not. By contrast, a third series of experiments demonstrated that perfusion of these antagonists (100 microM) locally into the cortex (through the probe) did not affect FG 7142-stimulated acetylcholine efflux. Moreover, none of these dopamine receptor antagonists, whether administered systemically or perfused into the nucleus accumbens or cortex, affected basal cortical acetylcholine efflux. These results reveal similarities in stimulated cortical acetylcholine release across frontal cortical regions and suggest a prominent role for D2-mediated accumbens dopamine transmission in the regulation of cortical acetylcholine release. The findings provide evidence in support of a neural substrate that links dysregulation of mesolimbic dopaminergic transmission to changes in cortical cholinergic transmission. Dysregulation within this circuit is hypothesized to contribute to the etiology of disorders such as schizophrenia, dementia and drug abuse.     

Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens.

We investigated whether D1 dopaminergic receptors modulate in vivo acetylcholine output in the shell and core areas of rat nucleus accumbens using the microdialysis technique. Subcutaneous injection (1, 2 and 3 mg/kg) of the D1 agonist SKF 82958 enhanced acetylcholine output in both areas of the nucleus accumbens while the selective D1 antagonist SCH 39166 (0.15 and 0.30 mg/kg, s.c.) lowered it. Both SKF 82958 and SCH 39166 were more effective in the shell than in the core region. The increase in acetylcholine release induced by SKF 82958 in the shell was tetrodotoxin-sensitive. The dopamine release inducer d-amphetamine (1 and 2mg/kg, s.c.) and the dopamine uptake inhibitor cocaine (10 and 20 mg/kg, i.p.) dose-dependently raised acetylcholine release in the shell and core areas. The dopaminergic stimulants, like the direct-acting D1 compounds, were more effective in the shell than in the core compartment of the nucleus accumbens. The acetylcholine increases in the shell induced by d-amphetamine (2 mg/kg), cocaine (20 mg/kg) and SKF 82958 (3 mg/kg) were antagonized by the D1 antagonists SCH 39166 (5 microM) and SCH 23390 (10 microM), applied locally by reverse dialysis. The results suggest that dopamine acting at the D1 receptors exerts a tonic stimulatory control over the cholinergic function of the shell and core compartments of the nucleus accumbens with the shell being more strongly influenced.     

Dopamine D1- and D2-receptor interaction in turning behaviour induced by dopamine agonists in 6-hydroxydopamine-lesioned rats

The selective dopamine D2-antagonist sulpiride potentiated contralateral circling behaviour induced by the D1-agonist CY 208-243 in rats with unilateral lesions of substantia nigra, but reduced the effects of the selective D2-agonist bromocriptine. Similarly, the D1-antagonist SCH 23390 tended to increase the effects of bromocriptine but markedly inhibited CY 208-243 induced turning. The mixed D1/D2-antagonist fluphenazine was effective in reducing circling behaviour induced by either agonist, whereas pimozide (D1/D2) inhibited only the actions of bromocriptine. These results indicate that the actions of CY 208-243 and bromocriptine are mediated via distinct but interacting receptor subtypes.     

Characterization of dopamine autoreceptors in the amygdala: a fast cyclic voltammetric study in vitro.

The present study has employed the technique of fast cyclic voltammetry to measure electrically-evoked dopamine release within the central amygdaloid complex in a rat brain slice. Local electrical stimulation caused the release of an electroactive substance which was identified, biochemically and pharmacologically, as being neuronal dopamine. Dopamine release could be inhibited by the dopamine D2 receptor agonist, quinpirole, but not by the D1 receptor agonist, SKF38393. Quinpirole-induced inhibitions were antagonized by sulpiride, metoclopramide and clozapine but not by SCH23390. It is concluded that dopamine release in the amygdala can be modulated by presynaptic D2 receptors which appear to be the same type as those found in striatum and nucleus accumbens.     

Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats.

D1 dopamine receptors are present on terminals of striatal neurons to the pars reticulata of the substantia nigra in the rat. Here we have studied the effect of the activation of these receptors on the synthesis of gamma-aminobutyric acid (GABA) in slices of the pars reticulata of the substantia nigra isolated from 6-hydroxydopamine-lesioned rats. The synthesis was judged by the accumulation of GABA after inhibiting GABA transaminase with aminooxyacetic acid. Both dopamine and SCH 23390, a D1 agonist, stimulated the synthesis. The effect of both compounds was blocked by SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. In the absence of receptor activation, the synthesis was very slow. The results suggest a trophic influence of dopamine upon the synthesis of GABA via D1 receptors.     

Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions

The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose, in particular the failure of the former to reduce bout size and the ability of the latter to induce a within-session decrement of bout number resembling either reward devaluation or neuroleptics on instrumental responding, we suggested that activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated on the basis of a dopamine D2-like receptor-mediated reward evaluation. Consistent results were obtained in a study examining the effect of dopamine D2-like receptor antagonism in rats licking for NaCl solutions and water. In this study, we examined the effects of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40 μg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15 M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60 s either after the first lick or after 3 min that the animals were placed in the chambers. Bout size, but not bout number, was decreased at the highest NaCl concentration. SCH 23390 produced a decrease of bout number and of lick number mainly due to the decreased number of subjects engaging in licking behaviour, and failed to reduce bout size for Na Cl and water at a dose which increased the latency to the 1st lick but did not affect the intra-bout lick rate. In agreement with previous observations, these results suggest that dopamine D1-like receptors play an important role in the activation of reward-oriented responses.     

Grooming behavior in mice induced by stimuli of corn oil in oral cavity

Mice show a strong preference for corn oil, which was thought to be elicited by stimulation in the oral cavity. Grooming behavior is known to be induced by dopamine D(1) stimulation in rodents. Therefore, we evaluated stimulation by corn oil in the oral cavity and the contribution of D(1) receptors to corn-oil-induced grooming in mice. Intraoral injection (0.1 ml) of corn oil induced grooming behavior similarly to SKF 38393 (10 mg/kg i.p.), a D(1) agonist, and both were antagonized by pretreatment with SCH 23390, a D(1) antagonist. However, a higher dose was needed for antagonism of the corn-oil-induced grooming compared with that induced by SKF 38393. Long-chain fatty acids, their methyl esters and alcohol, their triglycerides, mineral oil and silicone oil but not glycerin, a short-chain triglyceride, xanthan gum solution, or sucrose solution also induced grooming in mice. Xanthan gum solution, which was suggested to mask oil-like texture, attenuated the silicone-oil- but not corn-oil-induced grooming when injected intraorally as a mixture with an equal volume of the oil (50% suspension). The silicone-oil-induced grooming was reduced by SCH 23390 similarly to that induced by corn oil. These results suggested that stimulation by the oil-like texture in the oral cavity in mice induced grooming behavior and that it might be mediated at least partially via D(1) receptors. Moreover, stimuli other than texture might also contribute to the corn-oil-induced grooming.