Distinct Excitation to Pulpal Stimuli between Somatosensory and Insular Cortices.

Somatosensory information from the dental pulp is processed in the primary (S1) and secondary somatosensory cortex (S2) and in the insular oral region (IOR). Stimulation of maxillary incisor and molar initially induces excitation in S2/IOR, rostrodorsal to the mandibular incisor and molar pulp-responding regions. Although S1 and S2/IOR play their own roles in nociceptive information processing, the anatomical and physiological differences in the temporal activation kinetics, dependency on stimulation intensity, and additive or summative effects of simultaneous pulpal stimulation are still unknown. This information contributes not only to understanding topographical organization but also to speculating about the roles of S1 and S2/IOR in clinical aspects of pain regulation. In vivo optical imaging enables investigation of the spatiotemporal profiles of cortical excitation with high resolution. We determined the distinct features of optical responses to nociceptive stimulation of dental pulps between S1 and S2/IOR. In comparison to S1, optical signals in S2/IOR showed a larger amplitude with a shorter rise time and a longer decay time responding to maxillary molar pulp stimulation. The latency of excitation in S2/IOR was shorter than in S1. S2/IOR exhibited a lower threshold to evoke optical responses than S1, and the peak amplitude was larger in S2/IOR than in S1. Unexpectedly, the topography of S1 that responded to maxillary and mandibular incisor and molar pulps overlapped with the most ventral sites in S1 that was densely stained with cytochrome oxidase. An additive effect was observed in both S1 and S2/IOR after simultaneous stimulation of bilateral maxillary molar pulps but not after contralateral maxillary and mandibular molar pulp stimulation. These findings suggest that S2/IOR is more sensitive for detecting dental pulp sensation and codes stimulation intensity more precisely than S1. In addition, contra- and ipsilateral dental pulp nociception converges onto spatially closed sites in S1 and S2/IOR.

Sequential Changes in Cortical Excitation during Orthodontic Treatment.

Cortical excitation responding to periodontal ligament (PDL) stimulation is observed in the rat primary somatosensory (S1), secondary somatosensory, and insular oral region of the cortex (S2/IOR), which are considered to process somatosensation, including nociception. Our previous studies have demonstrated that excitatory propagation induced by PDL stimulation is facilitated in S1 and S2/IOR 1 d after experimental tooth movement (ETM), and tetanic stimulation of IOR induces long-term potentiation of cortical excitatory propagation consistently. These findings raise the possibility that ETM induces neuroplastic changes, and as a result, facilitation of cortical excitation would be sustained for weeks. However, no information is available about the temporal profiles of the facilitated cortical responses. We estimated PDL stimulation-induced cortical excitatory propagation in S1 and S2/IOR of rats by optical imaging 1 to 7 d after ETM of the maxillary first molar. ETM models showed facilitated cortical excitatory propagation in comparison with controls and sham groups 1 d after ETM, but the facilitation gradually recovered to the control level 3 to 7 d after ETM. Sham groups that received wire fixation without orthodontic force tended to enhance cortical responses, although the differences between controls and sham groups were almost insignificant. We also examined the relationship between cortical responses and expression of inflammatory cytokines, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, in PDL of the first molar. The peak amplitude of optical signals responding to PDL stimulation tended to be increased in parallel to the number of IL-1ß and TNF-α immunopositive cells, suggesting that, at least in part, the enhancement of cortical responses is induced by PDL inflammation. These findings suggest that ETM-induced facilitation of cortical excitatory propagation responding to PDL stimulation 1 d after ETM recovers to the control level within a week. The time course of the facilitated cortical responses is comparable to that of pain and discomfort induced by clinical orthodontic treatments.

Effects of NMDA and MK-801 injected into the substantia nigra pars reticulata on jaw movements evoked by dopamine D1-/D2 receptor stimulation in the ventrolateral striatum: studies in freely moving rats.

The effects of NMDA and MK-801 injected into the substantia nigra pars reticulata on jaw movements evoked by dopamine D1/D2 receptor stimulation in the ventrolateral striatum were examined in freely moving rats, by using a magnet-sensing system combined with intracerebral drug microinjection technique. Bilateral injections of a mixture of SKF 82958 (5 microg) and quinpirole (10 microg), agonist at dopamine D1 and D2 receptors respectively, into the ventrolateral striatum elicited repetitive jaw movements. Bilateral injections of NMDA (0.01 and 0.05 microg/0.2 microl in each side) into the substantia nigra pars reticulata, which alone did not produce jaw movements, reduced the repetitive jaw movements evoked by the dopamine D1/D2 receptor agonist mixture in a dose-dependent manner. Injection of the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.5 microg/0.2 microl in each side), into the substantia nigra pars reticulata, which alone did not produce jaw movements, prevented the dopaminergic jaw movements in a dose-dependent manner. Moreover, other behaviors such as grooming, rearing, yawning, vacuous chewing, and locomotor activity that occurred after injections of the dopamine receptor agonist mixture were not significantly altered by the bilateral injections of NMDA or MK-801 into the substantia nigra pars reticulata. Given our previous results showing that both agonist and antagonist of GABA(A) receptors injected into the substantia nigra pars reticulata inhibit the jaw movements elicited by dopamine D1/D2 receptor stimulation in the ventrolateral striatum, the present results suggest that there are complex functional interactions between NMDA and GABA(A) receptors within the substantia nigra pars reticulata that may be responsible for the common profiles in the effects of NMDA and GABA(A) receptor agents.

Orthodontic Force Facilitates Cortical Responses to Periodontal Stimulation.

Somatosensory information derived from the periodontal ligaments plays a critical role in identifying the strength and direction of occlusal force. The orthodontic force needed to move a tooth often causes uncomfortable sensations, including nociception around the tooth, and disturbs somatosensory information processing. However, it has mostly remained unknown whether orthodontic treatment modulates higher brain functions, especially cerebrocortical activity. To address this issue, we first elucidated the cortical region involved in sensory processing from the periodontal ligaments and then examined how experimental tooth movement (ETM) changes neural activity in these cortical regions. We performed in vivo optical imaging to identify the cortical responses evoked by electrical stimulation of the maxillary and mandibular incisor and the first molar periodontal ligaments in the rat. In naïve rats, electrical stimulation of the mandibular periodontal ligaments initially evoked neural excitation in the rostroventral part of the primary somatosensory cortex (S1), the ventrocaudal part of the secondary somatosensory cortex (S2), and the insular oral region (IOR), whereas maxillary periodontal ligaments elicited excitation only in S2/IOR rostrodorsally adjacent to the mandibular periodontal ligament-responding region. In contrast, maximum responses to mandibular and maxillary periodontal stimulation were observed in S1 and S2/IOR, and the 2 responses nearly overlapped. One day after ETM (maxillary molar movement by Waldo's method), the maximum response to stimulation of the maxillary molar periodontal ligament induced larger and broader excitation in S2/IOR, although the initial responses were not affected. Taken together with the histologic findings of IL-1ß expression and macrophage infiltration in the periodontal ligament of the ETM models, inflammation induced by ETM may play a role in the facilitation of S2/IOR activity. From the clinical viewpoints, the larger amplitude of cortical excitation may induce higher sensitivity to pain responding to nonnoxious stimuli, and enlargement of the responding area may reflect radiating pain.

Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.

A novel system was used to assess the role of D(1)-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D(1A) receptor knockout. Under spontaneous conditions, vertical jaw movements in wild-types declined with time at a rate that was reduced in D(1A) mutants, while horizontal jaw movements emerged progressively in wild-types but not in D(1A) mutants; tongue protrusions were absent in D(1A) mutants, while incisor chattering was initially reduced in D(1A) mutants but rose subsequently to reach the level of wild-types. D(1A) receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D(1A) mutants. These results suggest that D(1A) receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or that some D(1A) receptors might be coupled to a transduction system other than adenylyl cyclase.

Role of dopamine D1 and D2 receptors in the nucleus accumbens in jaw movements of rats: a critical role of the shell.

Given the differences in the dopamine neurotransmission between the shell and the core of the nucleus accumbens, as well as the differential involvement of these two domains in oral behaviour of rats, it was decided to determine whether or not dopamine D1 and/or dopamine D2 receptors differentially direct oral behaviour in these two domains in rats. Intra-accumbens injections of the dopamine D1 receptor agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine (SKF 82958: 5 micrograms/0.2 microliters), the dopamine D2 receptor agonist quinpirole (10 micrograms/0.2 microliters) and their combination were used to assess the role of these accumbens domains in jaw movements of rats. The present study shows that the combined administration of SKF 82958 and quinpirole into the shell, but not the core, of the nucleus accumbens produced a highly significant increase in jaw movements, when doses which per se were nearly ineffective, were injected. This effect was fully inhibited by prior administration of either the dopamine D1 receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 0.5 microgram/0.2 micrograms) or the dopamine D2 receptor antagonist (-)-sulpiride (25 ng/0.5 microliter) into the same region. It is concluded that dopamine D1 and D2 receptors in the shell, but not the core, of the nucleus accumbens are involved in jaw movements of the rat, providing the first piece of evidence that dopamine D1 and D2 receptors in the shell of the nucleus accumbens mediate a particular behaviour.

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; jaw movements.

The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of jaw movements in rats. When combined with the dopamine D1 receptor agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1- phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine (SKF 82958, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 10 micrograms) produced repetitive jaw movements following injection into the shell, but not the core, of the nucleus accumbens. This behaviour was only partially inhibited by local blockade of dopamine D1 receptors (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390, 500 ng), dopamine D2 receptors (domperidone, 50 and 100 ng) or dopamine D2/3 receptors (l-sulpiride, 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell completely antagonized the jaw movements elicited by the cocktail of SKF 82958 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist, S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[I]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did not produce jaw movements, when administered into the shell. Injection of the cocktail of SKF 82958 and 7-OH-DPAT into the ventrolateral striatum, which contains nearly no dopamine D3 receptors, also elicited jaw movements. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific jaw movements: the contribution of 7-OH-DPAT in the cocktail of SKF 82958 and 7-OH-DPAT to the display of jaw movements is solely due to its ability to activate dopamine D2 receptors.

Dorsal striatal mechanisms involved in the dopamine D2 receptor-mediated potentiation of apomorphine-induced jaw movements.

The role of dorsal striatal mechanisms in the regulation of apomorphine-induced jaw movements was studied. Jaw movements induced by apomorphine (0.2 mg/kg i.v.) were potentiated by quinpirole (10 micrograms/0.2 microliter) injected into the dorsal part of the striatum 10 min before apomorphine. Quinpirole injection into the ventral part of the striatum did not affect the effects of apomorphine. the quinpirole-induced potentiation in the dorsal striatum was prevented by l-sulpiride (25 ng), nemonapride (1 microgram), SCH23390 (1 microgram) or methylscopolamine (1 microgram), but not muscimol (50 ng), co-administered with quinpirole. Injection of these drugs alone 10 min before apomorphine failed to alter the effects of apomorphine. l-Sulpiride (25 ng) injected into the dorsal striatum 60 min before apomorphine increased the frequency of jaw movements induced by apomorphine (0.2 mg/kg). The l-sulpiride-induced potentiation was prevented by methylscopolamine (0.1 microgram) or l-sulpiride (25 ng) injected into the dorsal striatum 10 min before apomorphine; we had already found that this potentiation was also blocked by SCH23390. It is suggested that a synergistic dopamine D1/D2 receptor interaction underlies both the quick-onset potentiation by quinpirole and the delayed-onset potentiation by l-sulpiride.

Dopamine D-1 but not D-2 receptor stimulation of the dorsal striatum potentiates apomorphine-induced jaw movements in rats.

The effects of bilateral injections of selective D-1 and D-2 agonists and antagonists into the dorsal striata on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A phototransducer attached to the lower mandible automatically detected jaw movements. YM-09151-2 (0.2 and 0.5 micrograms) and cis(Z)-flupentixol (0.5 and 1 microgram) injected into the dorsal striatum increased the frequency of jaw movements after apomorphine (0.2 mg/kg i.v.). The effects were prevented by administration of SCH23390 (1 microgram) with YM-09151-2 (0.5 microgram) or cis(Z)-flupentixol (1 microgram). Injection of SCH23390 (1 microgram) alone into the dorsal striatum failed to alter the apomorphine (0.5 mg/kg i.v.)-induced jaw movements. Local application of the selective D-1 agonists, SKF38393 (5 micrograms) and SKF75670 (10 micrograms), into the dorsal striatum potentiated the apomorphine (0.2 mg/kg i.v.)-induced jaw movements, while a D-2 agonist, quinpirole (10 micrograms), injected into the same site attenuated these movements. These data are suggestive of an oppositional D-1: D-2 receptor interaction in the dorsal striatum.

Effects of dopamine D1 and D2 agonists and antagonists injected into the nucleus accumbens and globus pallidus on jaw movements of rats.

The effects of bilateral injections of selective D1 and D2 agonists and antagonists into the anteromedial part of the nucleus accumbens and the globus pallidus on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. Both SCH 23390 (0.1 and 1 micrograms) and 1-sulpiride (5 and 25 ng) injected into the nucleus accumbens suppressed the display of jaw movements after apomorphine (0.5 mg/kg i.v.). Injection of 1-sulpiride (5 and 25 ng) into the globus pallidus also blocked the effect of apomorphine, whereas SCH 23390 (1 microgram) injected into the same site was ineffective in this respect. Simultaneous application of the selective D1 and D2 agonists, SKF (1 or 5 micrograms) + quinpirole (10 micrograms), into the nucleus accumbens strongly potentiated the effect induced by local administration of each drug alone; a comparable, but smaller, effect was seen after simultaneous injections of these agents into the globus pallidus. These results show that dopaminergic mechanisms within the nucleus accumbens are involved in apomorphine-induced jaw movements, and that the expression of these movements requires concurrent activation of D1 and D2 receptors.

Cholinergic/dopaminergic interaction in the rat striatum assessed from drug-induced repetitive oral movements.

The role of striatal dopaminergic/cholinergic interactions in the regulation of oral behaviour in rats was studied using methods which resolve distinct patterns of jaw movements, allowing a more accurate quantitative and qualitative analysis. Both dopamine and acetylcholine receptor agonists given either systemically or into the ventral striatum induced repetitive oral movements. However, the cholinergic movements differed from dopaminergic movements as to pattern of activity. Oral movements induced by apomorphine (0.2 mg/kg i.v.) were potentiated by carbachol (0.1 microgram/0.2 microliters) injected into the dorsal striatum, while inhibition was observed when carbachol was injected into the ventral striatum. Pilocarpine (4 mg/kg)-induced oral movements were reduced by injecting flupentixol (10 micrograms/0.2 microliters), but not a combination of SKF 38393 (3 micrograms)+quinpirole (10 micrograms/0.2 microliter), into either the dorsal or the ventral striatum. Oral movements induced by the injection of carbachol (1 microgram/0.2 microliter) into the ventral striatum were enhanced by previous injection of this combination of dopamine receptor agonists into the same site and were inhibited by flupentixol. These results suggest that cholinergic and dopaminergic oral movements are separate behaviors and that the striatal dopamine/acetylcholine interaction in their regulation is neither simply antagonistic or synergistic, nor reciprocal.

Cholecystokinin octapeptide and caerulein injection into the dorsomedial nucleus accumbens potentiate apomorphine-induced jaw movements in rats.

The effects of bilateral intra-accumbal and intrastriatal injections of CCK-8 sulphate and its analogue, caerulein, on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were detected by a photo-transducer attached to the mandible. CCK-8 (5, 10 and 20 ng) and its analogue, caerulein (1 and 5 ng), injected into the dorsomedial nucleus accumbens increased the frequency of apomorphine (0.2 mg/kg i.v.)-induced jaw movements. The potentiation was prevented by administration of a CCK-A receptor antagonist, lorglumide (5 ng), together with CCK-8 (20 ng) or caerulein (5 ng). Injection of lorglumide alone into the dorsomedial nucleus accumbens did not alter apomorphine (0.5 mg/kg i.v.)-induced jaw movements. Injections of CCK-8 (20 ng) and caerulein (5 ng) into adjacent sites (the ventrolateral nucleus accumbens, dorsal striatum and ventral striatum) did not affect the responses elicited by apomorphine (0.2 mg/kg i.v.). These results demonstrate that CCK-8 modulates responses elicited by a dopamine receptor agonist, apomorphine, in a region of the brain where CCK-8 is known to co-exist with dopamine.

Functional interaction between dopamine D1 and D2 receptors in rat jaw movements.

The functional interaction between dopamine D1 and D2 receptors in dopamine-mediated jaw movements was studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were recorded by means of a light-emitting diode attached to the mandible; the method permits a detailed qualitative and quantitative analysis of jaw movements. D1 stimulation with SKF38393 (10 mg/kg i.v.) produced frequent bursts of teeth chattering, which were abolished by pretreatment with SCH23390 (0.25 mg/kg i.v.). D2 stimulation by quinpirole (1-10 mg/kg i.v.) produced infrequent bursts of jaw movements, which were characterized by low frequency jaw opening and closure movements from the rest position of the jaw, and absence of tongue protrusions. An additional stimulation of D1 receptors by giving SKF38393 30 min later produced an almost continuous pattern of jaw openings but less closure movements from the rest position, and the openings were accompanied by frequent tongue protrusions. These results clearly demonstrate that the type of oral behaviour produced by stimulation of D1 and D2 receptors together is qualitatively different from that produced by stimulation of either D1 or D2 receptors alone.

SK&F 83959 and non-cyclase-coupled dopamine D1-like receptors in jaw movements via dopamine D1-like/D2-like receptor synergism.

This study compared the effects of the dopamine D1-like receptor agents SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro- 1 H-3-benzazepine), which inhibits the stimulation of adenylyl cyclase, and A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman), a full efficacy agonist, in regulating jaw movements in the rat by synergism with dopamine D2-like receptor agonism. When SK&F 83959 and A 68930 were given in combination with quinpirole, there was a synergistic induction of jaw movements. Responsivity to SK&F 83959 + quinpirole was antagonised by the dopamine D1-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-ben zaz epine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl- 1,2,3,4-tetrahydroisoquinoline); synergism was antagonised also by the dopamine D2-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-++ +methyl-aminobenzamide). Responsivity to A 68930 + quinpirole was enhanced by low doses of SCH 23390, BW 737C and YM 09151-2, and antagonised by higher doses of SCH 23390 and YM 09151-2. These results implicate a novel, dopamine D1-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and suggest that its functional role extends to the regulation of jaw movements by synergistic interactions with dopamine D2-like receptors.

YM-14673, a thyrotropin-releasing hormone analogue, injected into the nucleus accumbens and the striatum produces repetitive jaw movements in rats.

Bilateral injections of the thyrotropin-releasing hormone (TRH) analogue, N alpha-[((S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate (YM-14673, 0.1 microgram and 1 microgram/0.2 microliters), into the nucleus accumbens, the dorsal and ventrolateral striatum produced repetitive jaw movements in a dose-dependent manner. The effects were greatest in the nucleus accumbens and smallest in the ventrolateral striatum. Pattern of the movements differed from that produced by injections of a mixture of SKF 38393 (5 micrograms) and quinpirole (10 micrograms); frequent tongue protrusions were evident in rats treated with the mixture but those were not seen in YM-14673-treated rats. TRH (1 microgram, 10 micrograms and 30 micrograms/0.2 microliters) did not evoke jaw movements from any of the sites. The non-selective dopamine receptor antagonist, cis-(Z)-flupentixol (10 micrograms), significantly reduced the response to administration of YM-14673 (1 microgram) into the nucleus accumbens or dorsal striatum, while the 5-hydroxytryptamine (5-HT)2A receptor antagonist, 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride (ICI 169,369, 0.2 micrograms), did not affect the response to YM-14673 (1 microgram). Given intrathecally (0.5 microgram/5 microliters), both YM-14673 and TRH produced wet-dog shakes. Although the mechanisms giving rise to the display of jaw movements after intrastriatal injections of YM-14673 remain unknown, stimulation of the dopamine D1/D2 receptors may at least partly contribute to these effects. Anyhow, these mechanisms differ from that underlying the ability of YM-14673 and TRH to elicit wet-dog shakes, a mechanism that is known to involve serotonergic processes.

Topographical assessment and pharmacological characterization of orofacial movements in mice: dopamine D(1)-like vs. D(2)-like receptor regulation.

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D(1)-like vs. D(2)-like receptors in their regulation. The dopamine D(1)-like receptor agonists A 68930 ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D(1)-like receptor antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D(2)-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D(1)-like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D(1)-like:D(2)-like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.

Ventral striatal vs. accumbal (shell) mechanisms and non-cyclase-coupled dopamine D(1)-like receptors in jaw movements.

This study compared the effects of intracerebral injections of the dopamine D(1)-like receptor agents 3-methyl-6-chloro-7,8-dihydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 83959) and [R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) into the ventrolateral striatum or the shell of the nucleus accumbens on the synergistic induction of jaw movements by intravenous (i.v.) co-administration of [R]-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 38393) or SK&F 83959 with the dopamine D(2)-like receptor agonist, quinpirole. In the ventrolateral striatum, SCH 23390 and SK&F 83959 each blocked jaw movements induced by i.v. SK&F 38393 with quinpirole, while only SCH 23390 blocked i.v. SK&F 83959 with quinpirole. SCH 23390 was less effective in the accumbens shell than in the ventrolateral striatum, and SK&F 83959 was ineffective to block i.v. SK&F 38393 with quinpirole, while neither SCH 23390 nor SK&F 83959 blocked i.v. SK&F 83959 with quinpirole. As SK&F 83959 inhibits the stimulation of adenylyl cyclase via dopamine D(1A) receptors but acts as an agonist at a putative dopamine D(1)-like receptor site not linked to cyclase, an important role is indicated for non-cyclase-coupled dopamine D(1)-like receptor sites as well as dopamine D(1A) receptors in the regulation of jaw movements via dopamine D(1)-like/D(2)-like receptor synergism, particularly in the ventrolateral striatum.

Further evidence for a functional dorsal-ventral division of the rat striatum: GABAergic involvement in oral movements.

Interactions between the gamma-aminobutyric acid (GABA)ergic system and the dopaminergic and cholinergic systems in the control of jaw movements, measured with a phototransducer system, were investigated in both dorsal and ventral regions of the rat striatum. Muscimol (25 and 50 ng/0.2 microliters) injected into the dorsal striatum did not affect jaw movements induced by apomorphine (0.2 mg/kg i.v.) or pilocarpine (4 mg/kg i.v.), but when injected into the ventral striatum it inhibited these jaw movements and those induced by carbachol (1 micrograms/0.2 microliters) injected into the ventral striatum. Picrotoxin (250 and 500 ng/0.2 microliters) injected into the dorsal striatum enhanced the effects of apomorphine (0.2 mg/kg) but not those of pilocarpine. When injected into the ventral striatum, picrotoxin did not affect apomorphine-induced oral movements but enhanced the effects of pilocarpine and carbachol. The benzodiazepine, flunitrazepam (100 ng/0.2 microliters), had no effect when injected in the dorsal striatum, and showed some inhibitory effects on dopaminergic and cholinergic oral movements when injected in the ventral striatum. The results suggest that the striatal GABAergic inhibitory effect on dopaminergic and cholinergic function is regionally specific, supporting a dorsal/ventral functional division of the rat striatum. The results also suggest that oral movements induced by dopaminergic and cholinergic drugs are distinct forms of repetitive oral behaviour.

Clozapine injected into the nucleus accumbens potentiates apomorphine-induced jaw movements.

The effects of clozapine injected into the nucleus accumbens on apomorphine-induced jaw movements were studied. Jaw movements induced by apomorphine (0.5 mg/kg i.v.) were potentiated by clozapine (10 micrograms/0.2 microliters) injected into the nucleus accumbens 10 min before apomorphine. Enhancement of the apomorphine-induced jaw movements was also found with the muscarinic acetylcholine receptor antagonist, methylscopolamine (2.5 micrograms), whereas the acetylcholine receptor agonist, carbachol (2.5 micrograms), inhibited the effects of apomorphine. Injection of a smaller dose of carbachol (0.1 microgram) alone into the nucleus accumbens 10 min before failed to alter the effects of apomorphine but prevented the potentiation induced by clozapine. Both the 5-hydroxytryptamine(5-HT)2A receptor antagonist, 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride (ICI 169,369, 0.1 and 0.2 microgram), and the alpha 1-adrenoceptor antagonist, prazosin (0.05 and 0.2 microgram), failed to affect the effects of apomorphine(0.5 mg/kg i.v.). In contrast, clozapine (1, 5 and 10 micrograms), ICI 169,369 (0.1 and 0.2 microgram) or prazosin (0.05 and 0.2 microgram) given into the ventral striatum inhibited the effects of apomorphine (0.5 mg/kg i.v.). It is suggested that the clozapine-induced potentiation in the nucleus accumbens might be due to its antimuscarinic properties.

Effects of intrastriatal injections of selective dopamine D-1 and D-2 agonists and antagonists on jaw movements of rats.

The effects of bilateral intrastriatal injections of the selective D-1 and D-2 antagonists, SCH23390 and sulpiride on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A photo-transducer attached to the lower mandible automatically detected jaw movements. Apomorphine (0.2, 0.5 and 1.0 mg/kg i.v.) dose dependently increased jaw movements, an effect prevented by prior administration into the ventral striatum of either SCH23390 (0.1, 0.5 and 1 microgram) or sulpiride (125 ng). To be effective, SCH23390 had to be given less than 30 min before apomorphine whereas sulpiride had to be given earlier. Sulpiride injected into the dorsal striatum potentiated the effects of apomorphine, an action prevented by administering the sulpiride with SCH23390. Local application of the selective D-1 and D-2 agonists, SKF38393 (5 micrograms) and quinpirole (10 micrograms) into sites within the ventral striatum from which repeated jaw movements could be obtained by electrical stimulation, also evoked jaw movements; the effects of combining the two drugs were much greater than the effects of either drug alone.