Hipovitaminosis D en pacientes hospitalizados por trastornos por consumo de sustancias en Unidad de Adicciones del Hospital Clínico Universidad de Chile / Hypovitaminosis D in patients hospitalized for substance use disorders in the Addictions Unit of the Hospital Clínico Universidad de Chile

The pathological consumption of alcohol and other drugs is associated with calcium metabolism disfunction through different pathways. Hypovitaminosis D contributes to acute a chronic neuronal injury in alcohol dependent patients. We do not have national evidence regarding the presence of hypovitaminosis D in addicted patients and there is a lack of information in the literature regarding polysubstance users. In this retrospective study, we evaluate the presence of hypovitaminosis of D in Substance Use Disorder inpatients treated in the Psychiatric Clinic of the University during the months of August to November 2017 and we described their main characteristics. 24 patients were evaluated, 19 of whom presented levels lower than 30 ng/ml of Vitamin D. Of those patients with hypovitaminosis 79% were men and 90% of them consumed alcohol, although in only 26% alcohol was the main substance. The main substance reported by the patients was cocaine (37%), smokable cocaine (32%) and marijuana (5%). Despite the methodological limitations of the study and the high prevalence of Hypovitaminosis D reported in the Chilean population, the results of this study suggest the need for a systematic evaluation of Vitamin D levels in patients hospitalized for addictions to adequately supplement those who require it. (AU)

Molecular and cellular regulation of hypothalamic melanocortin neurons controlling food intake and energy metabolism.

The brain receives and integrates environmental and metabolic information, transforms these signals into adequate neuronal circuit activities, and generates physiological behaviors to promote energy homeostasis. The responsible neuronal circuitries show lifetime plasticity and guaranty metabolic health and survival. However, this highly evolved organization has become challenged nowadays by chronic overload with nutrients and reduced physical activity, which results in an ever-increasing number of obese individuals worldwide. Research within the last two decades has aimed to decipher the responsible molecular and cellular mechanisms for regulation of the hypothalamic melanocortin neurons, which have a key role in the control of food intake and energy metabolism. This review maps the central connections of the melanocortin system and highlights its global position and divergent character in physiological and pathological metabolic events. Moreover, recently uncovered molecular and cellular processes in hypothalamic neurons and glial cells that drive plastic morphological and physiological changes in these cells, and account for regulation of food intake and energy metabolism, are brought into focus. Finally, potential functional interactions between metabolic disorders and psychiatric diseases are discussed.

[Surgery and management: natural partners]. / Chirurgie und Management: natürliche Partner.

The term management is a description of the functions: planning, organization, leadership and control in institutions and the corresponding persons holding these powers. In order to efficiently lead a department of surgery, surgeons need to possess management qualities and have to be able to act as team leaders. Good management of a surgical department leads to avoidance of complications and increased profits as well as more efficient use of operating room capacities and a better organization within the department.

[Is the determination of the defibrillation threshold in patients with an implantable cardioverter-defibrillator still required?]. / Wird die Bestimmung der Defibrillationsschwelle bei Patienten mit implantierbarem Kardioverter/Defibrillator noch benötigt?

BACKGROUND: Intraoperative testing of implantable cardioverter-defibrillators (ICDs) is time consuming and associated with risks. In the present study, we elucidated whether the initial implantation of an ICD with high energy output makes intraoperative defibrillation threshold testing (DFTT) unnecessary even though antiarrhythmic (AA) therapy is needed in the future. METHODS: A total of 111 patients (94 men, 17 women) receiving an ICD with subsequent AA therapy (mexiletine, amiodarone, sotalol, flecainide) were analyzed retrospectively. DFT was performed during ICD implantation and after AA drug therapy. In a second step, DFT results from the study cohort were analyzed for implantation of virtual ICDs with either low (≤ 30 J, LOD), intermediate (34 J, IOD), or high energy output (36 J, HOD). RESULTS: In the study cohort, all patients reached the safety margin (SM) of 10 J between DFT and maximal shock energy of the ICD. After loading of AA agents, 6 patients (12%) with a LOD, 3 patients (11%) with an IOD, and 3 (13%) patients with a HOD failed the 10 J SM. Using virtual ICDs, 6 (5.5%) patients with a LOD, 1 patient (1%) with an IOD, and no patients with a HOD would have failed the 10 J SM. After loading of AA agents, 18 patients (16%) with a virtual LOD, 12 patients (10.8%) with an IOD, and still 9 patients (8%) with a HOD would have failed the 10 J SM. CONCLUSION: Our results demonstrate that the 10 J SM would have been achieved intraoperatively in all patients with virtual HOD ICDs. Thus, determination of the DFT during implantation does not seem to be obligatory. However, in patients receiving AA agents, DFT testing is still required.

Identification of novel striatal genes by expression profiling in adult mouse brain.

Large-scale transcriptome analysis in the brain is a powerful approach to identify novel genes of potential interest toward understanding cerebral organization and function. We utilized the microarray technology to measure expression levels of about 24,000 genes and expressed sequence tags in mouse hippocampus, frontal cortex and striatum. Using expression profile obtained from whole brain as a reference, we categorized the genes into groups of genes either enriched in, or restricted to, one of the three areas of interest. We found enriched genes for each target area. Further, we identified 14 genes in the category of genes restricted to the striatum, among which were the orphan G protein-coupled receptor GPR88 and retinoic acid receptor-beta. These two genes were already reported to be selectively expressed in the striatum, thus validating our experimental approach. We selected 6 striatal-restricted genes, as well as 10 striatal-enriched candidates, that were previously undescribed. We analyzed their expression by in situ hybridization analysis in the brain, and quantitative RT-PCR in both brain and peripheral organs. Two of these unknown genes displayed a notable expression pattern. The striatal-restricted gene H3076B11 shows uniform expression throughout and uniquely in the striatum, representing a genuine striatal marker. The striatal-enriched gene 4833421E05Rik is preferentially expressed in the rostral striatum, and is also abundant in kidney, liver and lung. These two genes may contribute to some of the many striatal-controlled behaviors, including initiation of movement, habit formation, or reward and motivation.

Double-blind study on materials testing with applied kinesiology.

Applied Kinesiology (AK) is a scientifically unproven method used in complementary medicine to recognize the (in)tolerance of dental materials. Test-retest reliability of AK was examined. The working hypothesis was the assumption that the reliability of AK would not exceed random chance. Two dentists qualified in AK examined 112 volunteers to determine individual (in)tolerance toward two dental composite materials. After the first examination, 31 subjects were excluded from further testing. At the end of the open test phase, 34 of 81 participants had been classified as "tolerant", and seven as "intolerant" to both materials. The remaining 40 individuals showed a combination of either tolerant (to material I)/intolerant (to material II), or the reverse (n = 20 each). Retrieval rate was tested under blind conditions. In 14 cases, the results of the open and blinded tests matched, whereas in 26 cases they did not (95% confidence interval, 21%-52%; p = 0.98). This outcome confirmed our working hypothesis.

Biochemical disease-free survival in patients with a high prostate-specific antigen level (20-100 ng/mL) and clinically localized prostate cancer after radical prostatectomy.

OBJECTIVE: To examine our experience with radical prostatectomy (RP) in patients with a serum prostate-specific antigen (PSA) level of > 20 ng/mL (who are sometimes considered poor candidates for RP) to determine the outcome and possible predictors of a favourable outcome. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 79 patients who underwent RP with an initial PSA of 20-100 ng/mL. Biochemical disease-free survival (BDFS) was assessed using the Kaplan-Meier method and predictors of treatment outcome examined by uni- and multivariate analysis. Patients excluded from the analysis were 11 (14%) whose surgery was aborted after finding cancerous pelvic nodes and who did not undergo RP; four others with normal nodes during RP who had metastatic tumour on permanent sections; and 14 who had follow-up data for < 2 years. RESULTS: The mean (sd) age of the 50 patients in the final study population was 63 (7) years and the mean PSA 37.9 (16.0) ng/mL. The median (range) follow-up was 54 (24-120) months. The BDFS was 60% at 3 years and 48% at 5 years of follow-up. Two patients developed a local recurrence and eight developed metastatic disease. On logistic regression analysis of factors influencing BDFS, only extracapsular extension of disease was predictive of PSA recurrence; no preoperative factor was significant. When time to PSA recurrence was assessed by Cox regression analysis, again only extracapsular extension was predictive, with no preoperative variable a statistically significant predictor. CONCLUSIONS: Patients with a high serum PSA level (20-100 ng/mL) may be appropriate candidates for RP. While the cancer-free survival is not as good as in patients with a lower PSA, a significant percentage of patients achieve BDFS. No preoperative variables were predictive of disease-free survival or time to PSA recurrence.

Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine.

RATIONALE: Repeated administration of psychoactive drugs results in a progressive enhancement of the behavioral effects of these compounds, a phenomenon termed sensitization. OBJECTIVE: We tested whether repeated administration of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) induces sensitization of the disruptive effects of this compound on prepulse inhibition (PPI) of startle. METHODS: Rats received nine daily i.p. injections of 0.1 mg/kg MK-801 in the startle cage and were tested for PPI, startle in the absence of prepulses and motor activity in the startle cage. Another group of rats received MK-801 in the home cage on 9 days without daily testing. Controls were injected with saline and tested daily, while a separate group of rats received saline in the home cage without daily testing. On day 10, all rats received saline injections and were tested. On day 11, all rats were injected with 0.1 mg/kg MK-801 and tested again. On day 12, all rats received 1 mg/kg dl-amphetamine i.p. and were tested for PPI, to assess a possible cross-sensitization. RESULTS: MK-801 had no effect on day 1 of testing but induced a PPI deficit after 6-9 days of daily treatment and testing in those rats that received the drug in the startle cage, but not in the home cage. Motor activity was increased after repeated treatment and testing. There was also a trend towards sensitization of enhancement of the startle magnitude by MK-801 in these rats. dl-Amphetamine reduced PPI in those rats that received daily MK-801 injections in the startle cage to a similar extent as saline injections. CONCLUSIONS: Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.

The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats.

Glutamate receptors play an essential role in fear-related learning and memory. The present study was designed to assess the role of the group I metabotropic glutamate receptor (mGluR) subtype 5 in the acquisition and retrieval of conditioned fear in rats. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) was applied systemically (0.0, 0.3, 3.0, 30.0 mg/kg per os) 60 min before the acquisition training and before the expression of conditioned fear, respectively, in the fear-potentiated startle paradigm. MPEP dose-dependently blocked the acquisition of fear. This effect was not due to state-dependent learning. MPEP also prevented the expression of fear at a dose of 30.0 mg/kg. As a positive control for these effects, we showed that the benzodiazepine anxiolytic compound diazepam (1.25 mg/kg intraperitoneally) also blocked acquisition and expression of fear potentiated startle. MPEP did not affect the baseline startle magnitude, short-term habituation of startle, sensitisation of startle by footshocks or prepulse inhibition of startle. These data indicate a crucial role for mGluR5 in the regulation of fear conditioning. In the highest dose MPEP might exert anxiolytic properties.

A screen for mutations in human homologues of mice exencephaly genes Tfap2alpha and Msx2 in patients with neural tube defects.

BACKGROUND: Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing neural tube. METHODS: A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRalpha, and PAX1 already shown to be related to NTD. RESULTS: Two TFAP2alpha point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57-5.39). CONCLUSIONS: Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases.

Blockade of NMDA receptors in the amygdala prevents latent inhibition of fear-conditioning.

The association between a conditioned stimulus (CS) and an unconditioned stimulus (US) in fear-conditioning depends on N-methyl-D-aspartate (NMDA) receptors in the basolateral amygdala complex (BLA). Latent inhibition (LI) is the retardation in learning due to nonreinforced presentation of the prospective CS before conditioning. Disruption of LI in rats is an animal model of schizophrenia, reflecting the deficits of schizophrenic patients in neglecting irrelevant information. We investigated whether the BLA is involved in LI of fear-potentiated startle. Infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5; 12.5 nmoles) into the BLA before preexposure of rats to the neutral stimulus prevent LI of fear-conditioning. We also demonstrated by the same method that a complex of thalamic nuclei, comprising the medial part of the medial geniculate nucleus, the posterior intralaminar nucleus, and the suprageniculate nucleus, is involved in fear-conditioning, but not in LI. This suggests that the presentation of an innocuous stimulus during preexposure leads to an NMDA receptor-dependent change of neurotransmission in the BLA, but not in the thalamus. Our data show that the BLA but not the thalamus regulates in LI of fear-potentiated startle. Furthermore, it supports the hypothesis that the inability of schizophrenic patients to ignore irrelevant stimuli may be caused by hypofunction of the glutamatergic transmission in the brain and suggests an involvement of the amygdala in the neuropathology of schizophrenia.

Role of the substantia nigra pars reticulata in sensorimotor gating, measured by prepulse inhibition of startle in rats.

The substantia nigra pars reticulata (SNR) is one of the major output nuclei of the basal ganglia. It connects the dorsal and ventral striatum with the thalamus, superior colliculus and pontomedullary brainstem. The SNR is therefore in a strategic position to regulate sensorimotor behavior. We here assessed the effects of SNR lesions on prepulse inhibition (PPI) of the acoustic startle response (ASR), stereotypy and locomotion in drug-free rats, as well as after systemic administration of the dopamine agonist DL-amphetamine (2 mg/kg), and the NMDA receptor antagonists dizocilpine (0.16 mg/kg) and CGP 40116 (2 mg/kg). SNR lesions reduced PPI, enhanced spontaneous sniffing and potentiated the locomotor stimulation by dizocilpine and CGP 40116. PPI was impaired by dizocilpine and CGP 40116 in controls. The ASR was enhanced in controls by dizocilpine and amphetamine. SNR lesions prevented the enhancement of the ASR by amphetamine. A second experiment tested the hypothesis that the SNR mediates PPI via a GABAergic inhibition of the startle pathway. Infusion of the GABA(B) antagonist phaclofen but not the GABA(A) antagonist picrotoxin into the caudal pontine reticular nucleus reduced PPI. Hence, lesion of the SNR reduces sensorimotor gating possibly by elimination of a nigroreticular GABAergic projection interacting with GABA(B) receptors. Moreover, destruction of the SNR enhances the motor stimulatory effects of amphetamine and of the NMDA antagonists dizocilpine and CGP 40116. We conclude that the SNR exerts a tonic GABAergic inhibition on sensorimotor behavior that is regulated by the dorsal and the ventral striatum.

Early post-prostatectomy pelvic floor biofeedback.

PURPOSE: We determined whether biofeedback enhanced pelvic floor exercises begun 6 weeks after radical prostatectomy improve the early recovery of continence. MATERIALS AND METHODS: We randomized 30 patients who underwent radical retropubic prostatectomy into a group that received 5 biofeedback sessions and a control group. RESULTS: Overall 87% of patients were pad-free at 6 months with similar results in the treatment and control groups (86% versus 88%). There was no statistically significant difference in pad test results or voiding diary records in the 2 groups. CONCLUSIONS: A treatment program of biofeedback enhanced pelvic floor exercises begun 6 weeks after radical retropubic prostatectomy did not significantly affect continence in this study.

The neurobiology of startle.

Startle is a fast response to sudden, intense stimuli and probably protects the organism from injury by a predator or by a blow. The acoustic startle response (ASR) of mammals is mediated by a relatively simple neuronal circuit located in the lower brainstem. Neurons of the caudal pontine reticular nucleus (PnC) are key elements of this primary ASR pathway. The ASR in humans and animals has a non-zero baseline, that is, the response magnitude can be increased or decreased by a variety of pathological conditions and experimental manipulations. Therefore, the ASR has been used as a behavioral tool to assess the neuronal basis of behavioral plasticity and to model neuropathological dysfunctions of sensorimotor information processing. Cross-species examples for the increase of the ASR magnitude are sensitization, fear-potentiation and drug-induced enhancement. Examples for the reduction of the ASR magnitude are habituation, prepulse inhibition, drug-induced inhibition and the attenuation by positive affect. This review describes the neuronal basis underlying the mediation of the ASR, as well as the neuronal and neurochemical substrates of different phenomena of enhancement and attenuation of the ASR. It also attempts to elucidate the biological background of these forms of behavioral plasticity. Special emphasis is put on the potential relevance of ASR modulations for the understanding of human psychiatric and neurological diseases.

Cholinergic modulation of the acoustic startle response in the caudal pontine reticular nucleus of the rat.

The startle response is a useful behavioural model to assess drug effects on sensorimotor information processing in the mammalian central nervous system. Prepulse inhibition of the acoustic startle response in rats is an operational measure for sensorimotor gating mechanisms which may be necessary for attention and response selection. The caudal pontine reticular nucleus is a key element of the pathway that mediates the acoustic startle response and receives an inhibitory cholinergic projection that might be important for prepulse inhibition. The present study tested whether prepulse inhibition of acoustic startle is modulated by microinfusions of the muscarinic/nicotinic acetylcholine receptor agonist carbachol and of the muscarinic acetylcholine receptor antagonist scopolamine. Carbachol (0-40 nmol/0.5 microl) dose dependently attenuated startle and enhanced prepulse inhibition. Scopolamine (0-40 nmol/0.5 microl) dose-dependently enhanced startle and reduced prepulse inhibition at a dose of 10 nmol. Scopolamine (40 nmol) also increased the spontaneous motor activity of the rats. These findings lend support to the hypothesis that muscarinic acetylcholine receptors in the caudal pontine reticular nucleus inhibit the acoustic startle response and are involved in the mediation of prepulse inhibition of startle.

Lesions of the nucleus basalis magnocellularis do not impair prepulse inhibition and latent inhibition of fear-potentiated startle in the rat.

The present study tested if lesions of the nucleus basalis magnocellularis (NBM) affect prepulse inhibition (PPI) of the acoustic startle response and latent inhibition (LI) of fear-potentiated startle. The NBM is known to play an important role in learning and memory. Recently, the interest of research focused on its role in attentional and response selection processes. We here tested the effect of excitotoxic NBM-lesions on PPI, a phenomenon of sensorimotor gating that occurs at early stages of information processing. We also assessed the lesion effects on LI, a phenomenon of reduced conditioning after stimulus preexposure that can be used to measure selective attention. Bilateral infusions into the NBM of 80 nmol of quinolinic acid markedly reduced the number of choline acetyltransferase immunopositive neurons in the NBM and lead to a pronounced reduction of acetylcholine esterase in the cortex and the amygdala. However, no effects on PPI, fear-conditioning, or LI of fear-potentiated startle were found. Therefore, we conclude that there is no NBM-driven attentional or response selection process involved in PPI. Furthermore, the simple association learning in the classical conditioning paradigm used for fear-potentiated startle or LI is unaffected by NBM-lesions.

Regulation of sensorimotor gating by interactions of dopamine and adenosine in the rat.

Prepulse inhibition (PPI) of the acoustic startle response is a behavioural tool used to assess sensorimotor gating processes and its disturbances in rats and in humans. PPI in rats is reduced by an overactivity of the dopamine (DA) system. Because there are functional interactions between DA and adenosine receptors, we tested whether PPI can be influenced by the mixed DA receptor agonist apomorphine (APO) and by the unselective adenosine antagonist theophylline (THEO). Combined administration of APO (0.5 mg/kg, i.p.) and THEO (20 mg/kg, i.p.) in doses devoid of significant effects on their own significantly reduced PPI. The PPI-disrupting effect of the combined THEO plus APO treatment was dose-dependently antagonized by co-administration of the selective adenosine A1 agonist CPA (0.15-1.5 mg/kg, i.p.), but not by the A2A agonist CGS21680 (0.1-2 mg/kg, i.p.). These data demonstrate that antagonistic interactions between DA and adenosine, involving adenosine A1 receptors, play an important role in the regulation of PPI. The possible implications of these findings for the use of adenosine agonists in the treatment of schizophrenia are discussed.

Deficient sensorimotor gating following seizures in amygdala-kindled rats.

BACKGROUND: Human patients with limbic epilepsy may develop a psychosis. We combined animal models for epileptogenesis and schizophrenia to investigate possible mechanisms underlying the occurrence of psychoses in epileptics. Since the dysfunction of sensorimotor gating is the basis of some psychotic symptoms, we tested if epileptogenesis or acute seizures influence sensorimotor gating in rats, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is the reduction of the ASR that is observed when a startling pulse is preceded by a nonstartling prepulse. Reduced PPI was found in schizophrenics and in rats under certain conditions. METHODS: We investigated the effects on PPI of different models of limbic epileptogenesis (repeated stimulation of the basolateral amygdala, treatment with pentylenetetrazole, injection of kainate). RESULTS: PPI was normal in chronic epileptic rats 1 week after the last generalized seizure. Impaired PPI was found in amygdala-kindled rats 10 min after seizures. The ASR amplitude in the absence of prepulses was increased in kainate-treated rats, but not in the other groups. CONCLUSIONS: Chemical epileptogenesis or repeated stimulation of the amygdala per se did not disrupt sensorimotor gating, but the recent occurrence of seizures in amygdala-kindled rats compromised sensorimotor gating in a way compatible with psychotic states in humans.

Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population.

UNLABELLED: A number of recent studies have demonstrated that the occurrence and recurrence risk of neural tube defects (NTD) is reduced by folic acid supplementation before and during pregnancy. Epidemiological studies have shown low plasma folate and raised plasma homocysteine in women with spina bifida aperta (SB) children suggesting an abnormal folate metabolism. The 5,10-methylenetetrahydrofolate reductase (MTHFR) variant C677T, resulting in a decreased activity of the enzyme, has been associated with the development of NTD. Several studies demonstrated that homozygosity for the C677T mutation occurs at a higher frequency in patients with SB phenotype than in control individuals. The SB risk is strongest if both the mother and her child have the mutation in the homozygous state. In the present study we compared the frequency of the C- and T-alleles in healthy German individuals (n = 153) with German SB patients (n = 137). Our study groups reveal no significant difference in C/T-allele frequencies and genotype distributions. A family based association study, the transmission disequilibrium test, confirms the absence of an association between T-allele and SB. In 9 of 40 families we were able to exclude linkage to the MTHFR locus (1p36.3) employing different inheritance models. CONCLUSION: Our data show no evidence for an association between the C677T mutation and the occurrence of the SB phenotype. Therefore we cannot support the hypothesis that the MTHFR variant does account for a significant genetic predisposition to the SB phenotype in the studied German patients.

The ventral pallidum mediates disruption of prepulse inhibition of the acoustic startle response induced by dopamine agonists, but not by NMDA antagonists.

Prepulse inhibition (PPI) of the acoustic startle response is observed when the startling noise pulse is preceded by a weak, non-startling stimulus. PPI has been considered as a measure for sensorimotor gating mechanisms. Disruption of PPI can be found in schizophrenic patients as well as after blockade of NMDA receptors or stimulation of dopamine receptors in rats. The neuronal circuitry which regulates PPI consists of cortico-limbic brain structures where the nucleus accumbens (NAC) plays a key role. The NAC exerts its modulating effects on PPI by way of a projection from the ventral pallidum (VP) to the pedunculopontine tegmental nucleus (PPTg). We recently postulated that the reduction of PPI by intra-NAC infusion of glycine-site NMDA antagonists is not mediated by the VP. We tested here this hypothesis in rats with excitotoxic lesions of the VP which were systemically treated with apomorphine or MK-801 or received intraNAC infusions of dopamine or the glycine-site NMDA antagonist 7-chlorokynurenic acid. Lesioned rats showed a marked deficit in PPI after MK-801 and 7-chlorokynurenate treatment but not after apomorphine or dopamine injection, in contrast to sham-lesioned controls showing deficits in PPI under all conditions. These data provide behavioral evidence for the existence of a pathway which does not include the VP for the mediation of sensorimotor gating deficits. We propose that a direct connection between the NAC and PPTg may be responsible for the effects of NMDA/glycine receptor blockade, whereas the VP is an indispensable relay for the disruptive effects on PPI exerted by the NAC dopamine system.