Prefrontal cortex activity during swallowing in dysphagia patients.

Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z-scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food.

Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

AIMS: To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. METHODS: A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. RESULTS: Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. CONCLUSION: These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

Phosphorylation of p38 in Trigeminal Ganglion Neurons Contributes to Tongue Heat Hypersensitivity in Mice.

AIMS: To develop a tongue pain model with no mucosal pathologic changes and to examine whether phosphorylation of p38 in trigeminal ganglion (TG) neurons innervating the tongue is associated with tongue heat hypersensitivity in mice. METHODS: Tongue heat sensitivity in mice was assessed following application of the irritant 2,4,6-trinitrobenzene sulfonic acid (TNBS) to the tongue. After TNBS application, the expressions of p38, phosphorylated p38 (pp38), and transient receptor potential vanilloid 1 (TRPV1) were examined in TG neurons innervating the tongue. To further assess changes in tongue heat sensitivity and TRPV1 expression, a specific inhibitor of p38 phosphorylation (SB203580) was also administered into the TG. Student t test or two-way repeated-measures analysis of variance followed by Sidak multiple comparison test were used for statistical analysis, and P < .05 was considered statistically significant. RESULTS: TNBS application to the tongue induced noninflammatory heat hypersensitivity accompanied by the enhancement of p38 phosphorylation in TG neurons innervating the tongue and by an increase in the number of TRPV1 and pp38-immunoreactive (IR) TG neurons innervating the tongue. Intra-TG administration of SB203580 suppressed the increase in the TRPV1 and pp38-IR TG neurons and alleviated the noninflammatory tongue heat hypersensitivity induced by TNBS. CONCLUSION: p38 signaling cascades are involved in tongue heat hyperalgesia in association with TRPV1 upregulation in TG neurons innervating the TNBS-treated tongue.

Functional expression of BMP7 receptors in oral epithelial cells. Interleukin-17F production in response to BMP7.

BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-ß (TGF-ß) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells. METHODS: The expression of BMP receptors was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). OSCCs were stimulated with human recombinant BMP7 (hrBMP7) and the phosphorylation status of Smad1/5/8 was examined by western blotting. For microarray analysis, Ca9-22 cells were stimulated with 100 ng/mL of hrBMP7 and total RNA was extracted and subjected to real-time PCR. The 5'-untranslated region (5'-UTR) of IL-17 F gene was cloned to pGL4-basic vector and used for luciferase assay. Ca9-22 cells were pre-incubated with DM3189, a specific inhibitor of Smad1/5/8, for inhibition assay. RESULTS: All isoforms of type I and type II BMP receptors were expressed in both Ca9-22 and HSC3 cells and BMP7 stimulation resulted in the phosphorylation of Smad1/5/8 in both cell lines. The microarray analysis revealed the induction of interleukin-17 F (IL-17 F), netrin G2 (NTNG2) and hyaluronan synthase 1 (HAS1). Luciferase assay using the 5'-UTR of the IL-17 F gene revealed transcriptional regulation. Induced IL-17 F production was further confirmed at the protein level by ELISA. Smad1/5/8 inhibitor pretreatment decreased IL-17 F expression levels in the cells.

Satisfaction with dietary life affects oral health-related quality of life and subjective well-being in very elderly people.

Age-related deterioration in physical and oral health reduces healthy life expectancy and is thus an important problem for very elderly people. We investigated the effects of satisfaction with dietary life (SDL) in everyday life on oral health-related quality of life (OHRQoL) and subjective well-being and examined associations between these factors. We evaluated 426 elders aged 85 years or older. All participants completed a questionnaire that inquired about age, gender, drinking status, body mass index, cognitive function, disability, and comorbidities, among other covariates. Oral, physical, and mental health conditions were also examined. Associations of questionnaire results for SDL with items on subjective well-being (Philadelphia Geriatric Center Morale Scale [PGC] and World Health Organization-5 [WHO-5]) and OHRQoL (Geriatric Oral Health Assessment Index [GOHAI]) were confirmed with multiple logistic regression analysis. In a multivariate model adjusted for various confounders, participants with self-reported "enjoyable" SDL had significantly lower risks for having the lowest scores on the GOHAI, PGC, and WHO-5 (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.277-0.762; OR = 0.589, 95% CI = 0.348-0.996; and OR = 0.452, 95% CI = 0.263-0.775, respectively). These associations remained after further adjustment for number of teeth.

Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.

Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (<3%). pERK-NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain.

Perceived swallowing problems and mortality risk in very elderly people ≥85 years old: Results of the Tokyo Oldest Old Survey on Total Health study.

OBJECTIVE: The aim of this study was to clarify whether perceived swallowing problems affect the life expectancy of very elderly individuals. BACKGROUND: In an ageing society, oral function affects health status. In particular, a decline in swallowing function may increase the risk of various diseases, morbidity and malnutrition. MATERIALS AND METHODS: We evaluated 526 elderly individuals aged ≥85 years. All participants completed a questionnaire and underwent oral, physical and mental health examinations. The comprehensive oral health assessment comprised a face-to-face interview that included a questionnaire on swallowing function. We estimated hazard ratios and 95% confidence intervals using the Cox proportional hazards model, adjusting for potential confounders between perceived swallowing problems and all-cause mortality over a 3-year period. RESULTS: Over a 3-year follow-up period, 88 of 526 participants died and 68 participants complained of perceived swallowing problems. Perceived swallowing problems had statistically significant associations with physical status and function and nutrition. In the univariate analysis, perceived swallowing problems had statistically significant associations with an approximately 1.9-fold higher risk of all-cause mortality during the 3-year period (HR: 1.89, 95% CI: 1.14-3.14). In the multivariate analysis, the statistically significant association between perceived swallowing problems and all-cause mortality remained after adjusting for various confounding factors (HR: 1.73, 95% CI: 1.03-2.92). CONCLUSION: Perceived swallowing disorders should be verified by a clinical examination, as they are associated with other health outcomes and increased all-cause mortality.

Association between maximum occlusal force and 3-year all-cause mortality in community-dwelling elderly people.

BACKGROUND: Among the very elderly, poor oral health reduces life expectancy. In this study, differences in the magnitude of the maximum occlusal force (MOF) in the very elderly were examined in terms of effects on all-cause mortality in a 3-year follow-up. METHODS: We evaluated 489 community-living elderly individuals aged 85 years or older. MOF was measured using an occlusal force measuring device, and participants were classified into three groups according to gender- and dental status-sensitive tertiles. Demographic variables, cognitive, physical function, psychological status, oral health, comorbidity, and blood chemistry factors were assessed. One-way analyses of variance, χ (2) tests, and the Kruskal-Wallis test were used for statistical analyses. The relationship between MOF tertiles and 3-year all-cause mortality was examined using a multivariate Cox model analysis after adjusting for confounding factors. RESULTS: MOF tertiles were significantly associated with cognitive impairment, number of teeth, limitations on chewable foods, handgrip strength, timed up-and-go test, and diabetes mellitus. During the follow-up period, 74 subjects died. Subjects with the highest MOF had a significantly lower mortality rate than other groups (log rank P  =  0.031). In the univariate Cox model, MOF tertiles were independently associated with a lower risk of death (HR = 0.69, 95 % CI = 0.51-0.91). Even after adjusting for various confounders in the multivariate Cox model (Model 1), MOF was independently associated with a lower risk of death (HR = 0.67, 95 % CI = 0.50-0.91). In model 2, we added handgrip strength as a confounder and found that the HR for MOF was attenuated (HR = 0.73, 95 % CI = 0.54-0.99), but still statistically significant. CONCLUSIONS: In a cohort of the very elderly, MOF was independently associated with all-cause mortality after adjusting for various health issues. Moreover, this independent association remained after a further adjustment for handgrip strength; however, the HR was attenuated. This suggests that MOF and handgrip strength may share a common mechanism of a general decrease in muscle strength, possibly sarcopenia, which is a significant cause of mortality in the very old.

Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma.

Matrix metalloproteinases (MMPs) and tumor-associated macrophages (TAMs) play important roles in tumor growth. The present study investigated the expression levels of MMP2 and MMP9 in relation to the distribution of TAMs in the primary and metastatic regions of oral squamous cell carcinoma. Twenty-nine cases of oral squamous cell carcinoma (OSCC) with regional lymph node metastasis were selected from available documents in the archives of the Department of Pathology, Nihon University School of Dentistry. Four-micrometer-thick sections were prepared from the primary and metastatic regions. Each section was subjected to immunohistochemical staining using anti-MMP2, anti-MMP9, and anti-CD68 antibodies. The distribution and localization of MMPs and TAMs were compared between primary and metastatic regions. The expression levels of both MMPs were higher in the metastatic regions of lingual and gingival cancers. Statistically significant differences were observed in both T1 and T2 cases. In contrast to the higher expression of MMPs in metastatic regions, a higher number of TAMs were distributed in the primary regions. From these results, MMP expression levels and the numbers of TAMs were expected to have an inverse relationship between the primary and metastatic regions of OSCC. (J Oral Sci 58, 59-65, 2016).

Maximum occlusal force and physical performance in the oldest old: the Tokyo oldest old survey on total health.

OBJECTIVES: To elucidate the independent relationship between masticatory and physical performance in community-living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85-102). DESIGN: Cross-sectional analysis. SETTING: University research center or home-based examination. PARTICIPANTS: Four hundred eighty-nine community-living individuals (219 men, 270 women) aged 85 and older. MEASUREMENTS: Maximum occlusal force (MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C-reactive protein, interleukin (IL)-6, and total and free testosterone. RESULTS: MOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL-6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go (TUG) test in men and women (men: odds ratio (OR)=2.34, 95% confidence interval (CI)=1.02-5.38; women: OR=2.44, 95% CI=1.12-5.33). MOF was similarly associated with performance in chair standing, one-leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth. CONCLUSION: MOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age-related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men.

The Tokyo Oldest Old survey on Total Health (TOOTH): a longitudinal cohort study of multidimensional components of health and well-being.

BACKGROUND: With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study. METHODS/DESIGN: For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors. DISCUSSION: Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.

Short-term effects of oral appliances with equal bite-raising distance but with varying protrusions on occlusal force, contact area and load center.

The purpose of this study was to demonstrate how short-term wearing of an oral appliance (OA) with equal bite-raising distance but with varying protrusions affects occlusal force, contact area and load center. Twelve young healthy volunteers participated. With the appliance, the mandible was protruded 0%, 45%, 60% and 75% of maximum protrusion capacity, with 10 mm bite-raising between the first molars. The occlusal force, contact area and load center at maximum voluntary clenching were measured before wearing the OA, at 1 h, 3 h and 6 h during wearing, and 1 h after removal. When compared to the values before wearing the OA, occlusal force was significantly lower at 1 h, 3 h and 6 h during wearing in the case of no mandibular protrusion, and at 3 h and 6 h after for 45%, 60% and 75% of maximum mandibular protrusion (P < 0.05). Occlusal contact area was significantly smaller at 1 h and 6 h during wearing in the case of no protrusion, and at 6 h during wearing in the case of 45% of maximum protrusion (P < 0.05). There was a tendency for anterior shift in the location of the occlusal load center at 3 h and 6 h during wearing of the OA with any level of maximum protrusion. No significant change in these three measurements was found at 1 h after removal of the OA. The present study demonstrated that wearing an OA had only a marginal and transient influence on oral functions when their changes were compared before and after wearing the OA.

[Influence of oral appliances for obstructive sleep apnea syndrome on stomatognathic system part 1. Occlusion].

PURPOSE: Little information is available on the mandibular protrusion with oral appliances (OA) for the treatment of obstructive sleep apnea syndrome (OSAS) to have no negative effect on the stomatognathic system. The purpose of the current study was to assess the influence of mandibular protrusion on occlusion to fabricate the appropriate OA. METHODS: Twelve healthy adults were selected. With the OA in position, the mandible was advanced 0, 45, 60, 75% of maximum protrusion capacity; bite raising distance between the first molars was 5mm (OA5-0, 45, 60 and 75). The occlusal force, occlusal contact area and occlusal load center following maximum voluntary clenching for 5 seconds were investigated as follows: after wearing the OA for 1, 3 and 6 hours (Stage A1, A3 and A6) and 1 hour after removal (Stage R1). These data were compared with before wearing (Stage B). RESULTS: Occlusal force has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, at Stages A3 and A6 after wearing OA5-60, and at Stage A6 after wearing OA5-0. Occlusal contact area has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. Occlusal load center has significant forward displacement at Stages A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. CONCLUSION: To fabricate the appropriate OA in occlusal perspective, it is preferable to set the mandibular position at 45% advancement of maximum protrusion capacity of condyle head in terms of the mandibular positions used in this study.

Role of GABAA receptors in the endomorphin-1-, but not endomorphin-2-, induced dopamine efflux in the nucleus accumbens of freely moving rats.

In vivo microdialysis was used to study the effects of the locally applied GABA(A) receptor agonist muscimol and GABA(A) receptor antagonist bicuculline on the basal dopamine efflux as well as on the endomorphin-1- and endomorphin-2-induced dopamine efflux in the nucleus accumbens of freely moving rats. Muscimol (2500 pmol) and bicuculline (5 and 10 nmol) increased basal dopamine efflux. Bicuculline (50 pmol) inhibited the muscimol (2500 pmol)-induced dopamine efflux. Muscimol (250 pmol), but not bicuculline (50 and 500 pmol), enhanced the endomorphin-1 (25 nmol)-induced dopamine efflux. Bicuculline (50 pmol) counteracted the muscimol (250 pmol)-induced increase of the endomorphin-1-elicited dopamine efflux. Neither muscimol (25 and 250 pmol) nor bicuculline (50 and 500 pmol) affected the endomorphin-2 (25 nmol)-induced dopamine efflux. The doses mentioned are the total amount of drug over the infusion period (25 or 50 min) that varied across the drugs. The finding that muscimol and bicuculline increased basal dopamine efflux may imply that these drugs acted at different sites. It is suggested that (1) muscimol acts at GABA(A) receptors on GABA-ergic neurons that exert an inhibitory control of dopaminergic neurons and, accordingly, disinhibits these dopaminergic neurons, and that (2) bicuculline acts directly at GABA(A) receptors on dopaminergic neurons and, accordingly, removes the inhibitory control of these dopaminergic neurons. The finding that an agonist, but not antagonist, of GABA(A) receptors enhanced the endomorphin-1's effects might indicate that endomorphin-1 produced a floor effect at the level of GABA(A) receptors located on presynaptic, dopaminergic terminals. Finally, the present results support our earlier reported notion that endomorphin-1 and endomorphin-2 increase accumbal dopamine efflux by different mechanisms.

Phosphorylation of ERK in trigeminal spinal nucleus neurons following passive jaw movement in rats with chronic temporomandibular joint inflammation.

AIMS: To elucidate the neuronal mechanisms underlying chronic pain of the temporomandibular joint (TMJ), expression of phosphorylated extracellular signal-regulated kinase (pERK) in the trigeminal spinal nucleus caudalis (Vc) was studied in rats with a chronically inflamed TMJ. METHODS: Complete Freund's adjuvant (CFA) was injected in the left TMJ region of rats anesthetized with pentobarbital (50 mg/kg intraperitoneally). Face temperature of the TMJ region was measured periodically after CFA injection. Two weeks after CFA injection, passive jaw movement with 4-, 6-, and 15-mm distances was carried out in inflamed and naive rats for 5, 15, and 30 minutes. pERK expression was studied in the medulla and upper cervical cord after passive jaw movement. RESULTS: Face temperature was significantly increased 2 days after CFA injection and returned to the preoperative level 7 days later. The pERK-like immunoreactive (LI) cells were observed in the dorsal portion of the rostral Vc in inflamed rats after passive jaw movement, and a small number of pERK-LI cells were observed in naive rats after passive jaw movement. No pERK-LI cells were observed in the TMJ of inflamed rats without jaw movement. The number of pERK-LI cells increased following increases in the jaw-movement distance and duration. CONCLUSION: These findings suggest that the dorsal portion of the rostral Vc may be involved in mediating chronic pain following TMJ inflammation and that the intracellular ERK cascade may be involved.

Role of GABA(A) receptors in the retrorubral field and ventral pallidum in rat jaw movements elicited by dopaminergic stimulation of the nucleus accumbens shell.

The role of gamma-aminobutyric acid (GABA)(A) receptors in the retrorubral field in the production of rat repetitive jaw movements was examined, as this nucleus receives a GABAergic, inhibitory input from the nucleus accumbens and is connected with the parvicellular reticular formation, a region that is directly connected with the orofacial motor nuclei. The GABA(A) receptor antagonist bicuculline (150 ng/0.2 microl per side) significantly produced repetitive jaw movements when injected bilaterally into the retrorubral field, but not the ventral pallidum. The effects of bicuculline were GABA(A) receptor specific, because the effects were abolished by muscimol, a GABA(A) receptor agonist, given into the same site. The bicuculline-induced jaw movements differed qualitatively from those elicited by injection of a mixture of (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 82958; 5 microg) and quinpirole (10 microg), agonist at dopamine D1 and D2 receptors respectively, into the nucleus accumbens shell. Nevertheless, bilateral injections of muscimol (10 ng, 25 ng and 50 ng/0.2 microl per side) into the retrorubral field significantly inhibited jaw movements evoked by the dopamine D1/D2 receptor stimulation in the nucleus accumbens shell. Bilateral injections of bicuculline (50 ng and 150 ng/0.2 microl per side) also reduced the dopamine D1/D2 receptor-mediated jaw movements. Essentially similar effects were obtained when muscimol and bicuculline were given into the ventral pallidum, a region that is also known to receive GABAergic inhibitory inputs from the nucleus accumbens. In conclusion, GABA(A) receptor blockade in the retrorubral field elicits characteristic repetitive jaw movements, and the GABA(A) receptors in that region as well as in the ventral pallidum modulate the accumbens-specific, dopamine D1/D2 receptor-mediated jaw movements.