Prepulse inhibition (PPI) is the decrease of startle reflex amplitude when a slight stimulus is previously generated. This paradigm may provide valuable information about sensorimotor gating functionality. Here we aimed at determining the inhibited and uninhibited startle response of capuchin monkeys (Sapajus spp.), and to evaluate the role of the superior colliculus in PPI. Capuchin monkeys were tested in a whole-body protocol, to determine the best startle amplitude and interstimuli interval. Additionally we tested two subjects with bilateral superior colliculus damage in this protocol. Results show that 115 dB auditory pulse has induced the best startle response. In contrast to reports in other species, no habituation to the auditory stimuli was observed here in capuchins. Also, startle reflex inhibition was optimal after 120 msec interstimuli interval. Finally, there was a downward tendency of percentage inhibition in superior colliculus-lesioned monkeys. Our data provides the possibility of further studies with whole-body protocol in capuchin monkeys and reinforces the importance of the superior colliculus in PPI.
Citation: Saletti PG, Maior RS, Hori E, Almeida RMd, Nishijo H, Tomaz C (2014) Whole-Body Prepulse Inhibition Protocol to Test Sensorymotor Gating Mechanisms in Monkeys. PLoS ONE 9(8): e105551. https://doi.org/10.1371/journal.pone.0105551
Editor: Brenton G. Cooper, Texas Christian University, United States of America
Received: March 21, 2014; Accepted: July 23, 2014; Published: August 21, 2014
Copyright: © 2014 Saletti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.
Funding: This research was supported in part by the JSPS Asian Core Program and the Ministry of Education, Science, Sports, and Culture, Grant-in-Aid for Scientific Research (B) (25290005); and Research Support Foundation, FAP-DF, Brazil (2010/00154-0). PGS was recipient of a doctoral fellowship from CAPES and CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Acoustic startle reflex (ASR) is an innate response that causes a rapid contraction of facial and bodily muscles provoked by an intense and sharp noise , . ASR can be used as an experimental model for the study of sensitization, habituation, prepulse inhibition, fear potentiated startle, as well as to test the effects of drugs on behaviour –. Prepulse inhibition (PPI) paradigm is the decrease of ASR when a slight acoustic stimulus is previously generated , , . PPI depends on some stimuli-related variables, chiefly: intensity, duration, and interstimuli interval. This behavioural paradigm may provide valuable information about sensorimotor gating functionality. Understanding the neural circuitry underlying PPI may provide important insights into neurological disorders, such as schizophrenia . Indeed, PPI test is generally used as a screening procedure for substances with potential antipsychotic effects , . In this sense, tests in nonhuman primates are crucial since their results may be more readily extrapolated to humans due to brain and behavioural similarities between monkeys and human beings. Some PPI paradigm-studies have identified interstimuli intervals, as well as stimuli intensities and duration for some nonhuman primates , , .
Midbrain is essential for PPI , . In an experiment with rats Yeomans et al  suggested that the mesencephalic pathways are involved in acoustic PPI. They found that a fast auditory pathway from cochlear nucleus starting from inferior colliculus to the intercollicular nucleus, then it reaches intermediate layers of the superior colliculus (SC) and proceeds to tegmental pedunculopontine nucleus, which in turn projects to the basal ganglia and into the spinal cord. Yeomans et al  also emphasized a slower multisensory pathway started in SC intermediate layers. These results support previous studies that demonstrated the importance of such structures in PPI , . Although SC is involved in responses to visual stimuli, including detection of salient stimuli, head and eyes orientation, saccadic movements and shifts of attention –, this subcortical structure is strongly implicated in defensive behaviours –. In addiction, SC receives auditory inputs from inferior colliculus  that must be related to PPI . Therefore, SC is an important center of multisensory integration that receives visual, auditory, and somatosensory information from several cortical and subcortical areas –.
The present study aimed to determine the pattern of startle response of individuals of Sapajus spp. using whole-body protocol, to determine the best intensity and PPI interstimuli interval as well as to evaluate the role of the SC in capuchin monkeys in PPI.
Materials and Methods
All procedures involving animals had been conducted according to guidelines of the Brazilian Society of Animal Experimentation (COBEA) and followed the Principles of Laboratory Animal Care (NIH publication no. 85-23, revised 1996). This study was approved by the Animal Ethics Committee of the Institute of Biology, University of Brasilia (UnBDOC no 128181/2011). All experiments were conducted at Primate Center at University of Brasilia, Brazil.
Animals were pair-housed in cages with natural substrate, with rope swings and nest boxes, measuring 3×3×1.8 m, under natural conditions of lightness and temperature. Animals were given access to food and water ad libitum. New supply of food was offered twice daily, early morning and late in the day, and water was offered by automatic drinking fountain. Animals were under constant environmental enriching tasks as usual in our Primate Center. No animal was submitted to any kind of suffering. In order to minimize stress during experiments, animals were submitted to acclimation sessions (see below), in which they received fruits reward for quiet standing in test equipment. Since animals are still under behavioural studies, no individual has been euthanized after the present study.
A total of 12 capuchin monkeys (Sapajus spp.), 8 females and 4 males, weighing between 2 and 5 kg were employed in this study. Animals were submitted to test sessions after feed time between 8–12 am, five days a week.
Subjects were placed inside the experimental chamber (see description below) by an experimenter and were submitted to 5–8 sessions for acclimation. Animals remained for 60 min per day inside the chamber with 65 dB white noise on. During this period the monkeys received fruits reward for quiet standing. Similar procedure was used for 10 min before every test session.
Three different tests were performed in the following sequence: startle response amplitude, prepulse inhibition and superior colliculus lesion. In startle response amplitude test, 6 animals (4 females and 2 males) were employed. In prepulse inhibition test, all the same 6 subjects were employed and we added 2 females. The 8 subjects used in prepulse inhibition test were also employed in the SC-lesion test as a control group. Beyond these 8 subjects, we employed 2 females as the sham-group and 2 males as the lesion-group. All those tests are detailed below at next sections.
Tests were conducted in a room next to the house cage inside an acoustically isolated compartment (140×100×170 cm), with a permanent white noise of approximately 65 dB. A bottomless chamber measuring 60×30×30 cm was built in transparent acrylic material of 15 mm thick and placed above a wooden box measuring 45×40×40 cm (Fig. 1). This wooden box was built to keep the animal away from the ground improving the welfare of the subjects during tests. Subjects were placed inside the acrylic chamber with its head out. The top of the chamber had an adjustable hole that held the subjects neck. A device (30×30×25 cm) equipped with two speakers (Foster Model FT96H Frequency band; 4 KHz∼30 KHz) was placed above subject's head, whereas each speaker was 10 cm away from the head. Speakers were connected to a sound generator (O'Hara & Co., Ltd., Tokyo) and a video camera (Model Clone #1004124), which allowed continuous monitoring of the subject by an external computer during the procedure. Subject's whole-body movement were captured by an accelerometer (Inntechno Japan Co.ltd., Model: BDK3) located on the bottom of chamber and connected to an amplifier (O'Hara & Co., Ltd.). The whole system was connected to a recording software (Animal Startle – PCI 6024E, developed by O'Hara & Co., Ltd.), interfaced with Windows XP operational system, which allowed adjustment of some recording features.
Startle response amplitude
Six animals (two males and four females) were employed in this experiment. The startle amplitude was measured in a single session with 10 equal and consecutive blocks of 5 pseudorandom white noise stimuli each (90, 95, 100, 115, 120 dB). Inter-stimulus interval was 60 sec and the duration of each stimulus was 40 msec. Startle response was defined as the maximum peak voltage amplitude of the accelerometer over 400 msec after stimulus presentation. Basal activity was defined as the maximum peak voltage over 400 msec before stimulus presentation.
Eight animals (two males and six females) were employed on a single session of 7 equal and consecutive blocks of 7 pseudorandom trials each (pulse-alone, prepulse-alone and 5 prepulse-pulse trials ranging inter-stimulus intervals: 45, 70, 120, 520, 1020 msec). Pulse and prepulse were 115 dB and 80 dB white noise stimuli respectively and inter-trial interval was 60 sec. Startle response was recorded over 1800 msec after each presentation.
Superior colliculus lesion
PPI was conducted in two males submitted to bilateral neurotoxic lesions of the SC and two females that were submitted to SC-sham surgery. Ibotenic acid (IBO) was infused in four injection sites, two in each SC (10 mg/kg in phosphate-buffered saline (PBS); Sigma-Aldrich, St. Louis, MO, USA) at a rate of 1 µl/5 min not to cause mechanical damages on those structures. In each site 0.4–0.8 µl IBO was delivered and the glass pipette was left inside the brain for 2 min to allow the dispersion and to avoid reflux during removal. Injection sites were determined by means of a stereotaxic atlas for Sapajus . The SC-sham group was submitted to the same overall procedure, but instead IBO, the same volume of PBS vehicle was infused. For more details about surgery and evaluation of extent of injury, see Maior et al . We also submitted the same eight animals (control group) cited above to the PPI test described in this session. Animals were employed on a single session of 10 equal and consecutive blocks of 3 pseudorandom stimuli each (pulse-alone, 115 dB, 40 msec duration; prepulse-alone, 80 dB, 20 msec duration and pulse-prepulse, 120 msec interval). Startle response was recorded as maximum peak amplitude over 600 msec after each presentation.
Startle response amplitude.
One-factor repeated-measures analysis of variance (ANOVA) and post hoc Bonferroni test were performed to examine the effects of stimulus intensity on startle amplitude relative to basal activity, the startle response to different stimulus intensities and the mean startle response for all intensities along trial blocks.
The percent inhibition of the startle response was calculated for each subject by the following formula: 100× ([pulse-alone] - [prepulse-pulse])/(pulse-alone) as done in previous PPI studies , . One-factor ANOVA was performed using prepulse interval and trial block as within-subjects factors. Also a post hoc Bonferroni test was performed to examine individual main and interaction effects.
Superior colliculus lesion.
The details of the lesion were published elsewhere . IBO injections resulted in circumscribed bilateral lesions, characterized by cell loss filled with gliosis, identified as hypersignal in T-2weighed and FLAIR scans (2-mm thick images). The lesions encompassed all SC layers down to inferior colliculus and central gray and extended two-thirds of the rostrocaudal SC axis in all subjects. No discernible damage was found in the tissues above SC due to IBO leaking during cannula retraction. Percent inhibition was calculated as explained in session 2.6.2. A Kruskal-Wallis analysis comparing the means for each group was performed to compare the percentage inhibition of the startle response among lesion, sham-lesion and control groups.
Startle response amplitude
Acoustic startle response amplitude showed a gradual increase with increasing of stimulus intensity in the control monkeys. No difference was found in basal activity [F (0.81); p = 0.51]. There was no statistical difference over the course of 10 repeated trial blocks, showing that there was no habituation during the test trial [F (0.862); p = 0.55] (Fig. 2-A). Figure 2-B shows the mean amplitude startle response relative to baseline activity. All intensities caused greater startle responses than the basal activity (p<0.05). ANOVA followed by post hoc Bonferroni test indicated that only 90×95 dB and 115×120 dB intensities had no significant difference between themselves (p>0.05).
A – Mean relative startle responses, collapsed across stimulus intensities, across repeated blocks of test trials. B - Mean relative startle responses across repeated blocks. * basal activity vs. all acoustic intensities (90–120 dB); # no statistical difference. (n = 6).
There was no habituation over the course of 7 trial blocks in the control monkeys [F (0.99); p = 0.43] (Fig. 3-A). ANOVA followed by post hoc Bonferroni test indicated that only in prepulse-pulse 120 msec-interval trial mean amplitude was different of pulse-alone trial amplitude (p = 0.01). In all others cases, prepulse-pulse trials had the same response amplitude as pulse-alone trials (p>0.17). Also, prepulse-alone was different of pulse-alone response (p<0.01) (Fig. 3-B). Figure 3-C shows percentage of inhibition of startle response of each interstimulus interval tested.
A - Mean relative startle responses, collapsed across interstimulus intervals, across 7 blocks of test trials. B - Mean relative startle responses in each test situation. * difference of pulse-alone response (p<0.05). C – Mean relative percent of startle inhibition provoked by each interval between prepulse and pulse stimuli. (n = 8).
Superior colliculus lesions
There was no habituation over the course of 10 trial blocks for any of the groups [control: F (1.11); p = 0.15, sham: F (0.86); p = 0.57, lesion: F (1.19); p = 0.31] (Fig. 4-A). As seen in Fig. 4-B, Kruskal-Wallis analyses yielded no significant difference on percent inhibition between the three groups despite a tendency to deficit of prepulse inhibition in SC-lesion animals (x2 = 2.965; p = 0.227).
A – Mean relative startle responses, collapsed across the three test trials, across 10 blocks. B – Mean relative percent inhibition of startle response in control (n = 8), sham (n = 2) and lesion (n = 2) groups in prepulse-pulse 120 msec-interval protocol.
In the present study, we demonstrated startle response in Sapajus spp. in a whole-body paradigm. Our findings are consistent with the study accomplished by Winslow et al.  in rhesus monkeys, which revealed the possibility to evaluate Macaca startle pattern with the measurement of whole-body activity. Now we demonstrated that with the same protocol, capuchin and rhesus monkeys exhibit the same pattern of startle and PPI responses. To our knowledge there is only one previous report of PPI in capuchin monkeys. Linn and Javitt  adapted an eyeblink protocol apparatus for testing in humans and found similar results as the present study.
The pattern of PPI response followed expectations. We found that 115 dB and 120 dB were equally good to cause startle response. Considering that 115 dB was capable of inducing the expected response in our subjects and that it is also the same intensity found in literature for other primates , , , , this intensity was selected as startle intensity for the subsequent tests. As in other nonhuman primate species, a prepulse intensity of 80 dB was ideal to inhibit the startle response generated by an 115 dB pulse. Also, the interstimuli interval that best inhibited startle response was 120 msec, in keeping with previous reports in other nonhuman primates , , , .
In the SC-lesion test, we intended to evaluate our experimental protocol and test the role of SC on PPI response in primates. Thus, it was possible to show that there is a downward tendency of prepulse inhibition in animals with SC damage as well as demonstrated in rats , . Although caution should be taken when analysing this tentative study, the percentage inhibition found was not significant across the experimental groups. SC is an important and well-known structure related to visual information (for review ), however SC also receives multisensory information, such as tactile and auditory , , . SC deep layers are also related to defensive behaviours such as freezing, darting and shift of attention in rodents , , , as well as prey-predator behaviour in primates , . Therefore, further testing might lead to a better understanding of SC's role in nonhuman primate PPI.
Habituation is a learning process whereby behavioural responses decrease after repeated stimulations , . As seen in Figs. 2-A and 3-A, we observe a non-significant reduction of the startle amplitude during the session test, i.e., no habituation was observed. In humans, 13 trials are optimal to reduce behavioural responses with a 100 dB startle stimulus  and in rhesus monkeys a small decrease in startle amplitude has been observed after 5 blocks of stimuli presentation within session . Interestingly, deficits in startle habituation have been observed in schizophrenic patients , . Habituation in subjects with damage to the superior colliculus was also not observed (Fig. 4-A). Nevertheless, it is known that schizophrenia patients show deficits in habituation due to dysfunction on the hippocampus, which indicates that this reduction of behavioural response may be correlated with memory performance  and perhaps there is no relation with the superior colliculus. Regardless, the lack of habituation in observed here suggests that PPI testing on this species may help understand the habituation patterns seen in schizophrenic patients.
The validation of the PPI test with whole-body experimental protocol using capuchin monkeys enables new preclinical studies to test potential antipsychotic substances. Many studies have been conducted with rodents –, but due to Sapajus phylogenetic proximity with humans, the use of these animals as experimental models for drug testing may yield more reliable results.
The present study validates the PPI paradigm for testing in capuchin monkeys. Habituation to auditory stimuli was not seen here in Sapajus as reported in humans and rhesus. This was the first study that shows PPI responses of SC-lesioned primates, thus the results might be relevant to understand the role of the SC in humans' neurological disorders with impairment in sensorimotor gating mechanisms, as schizophrenia. Further validation of our experimental protocol enables future studies in order to find new antipsychotic drugs.
Startle response of animals in Startle response amplitude test.
Startle response of animals in Prepulse inhibition test.
We thank G.V. da Silva, A. Araujo, R.S. Oliveira and C.D. Azevedo for excellent animal care.
Conceived and designed the experiments: CT RSM PGS HN EH. Performed the experiments: PGS RSM EH. Analyzed the data: PGS CT RSM HN EH. Contributed reagents/materials/analysis tools: CT RSM PGS HN EH RMA. Contributed to the writing of the manuscript: CT RSM PGS HN EH RMA.
- 1. Lang PJ, Bradley MM, Cuthbert BN (1990) Emotion, attention, and the startle reflex. Psychol Rev 97: 377–395.
- 2. Braff DL, Geyer MA, Swerdlow NR (2001) Humans studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psycopharmacology 156: 234–258.
- 3. Li L, Korngut LM, Frost BJ, Beninger RJ (1998) Prepulse inhibition following lesions of the inferior colliculus: prepulse intensity functions. Physiol Behav 65: 133–139.
- 4. Koch M (1999) The neurobiology of startle. Prog Neurobiol 59: 107–128.
- 5. Winslow JT, Parr LA, Davis M (2002) Acoustic startle, prepulse inhibition, and fear-potentiated startle measured in rhesus monkeys. Biol Psychiatry 51: 859–866.
- 6. Winslow JT, Noble PL, Davis M (2007) Modulation of fear-potetiated startle and vocalizations in juvenile rhesus monkeys by morphine, diazepam, and buspirone. Biol Psychiatry 61: 389–395.
- 7. Hoffman HS, Ison JR (1980) Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input. Psychol Rev 87: 175–189.
- 8. Graham FK (1975) The more or less startling effects of weak prestimulation. Psychophysiology 12: 238–248.
- 9. Braff DL, Geyer MA, Light GA, Sprock J, Perry W, et al. (2001) Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr Res 49: 171–178.
- 10. Rigdon GC, Viik K (1991) Prepulse inhibition as a screening test for potential antipsychotics. Drug Develop Res 23: 91–99.
- 11. Swerdlow NR, Geyer MA (1993) Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia. Pharmacol Biochem Behav 44: 741–744.
- 12. Linn GS, Javitt DC (2001) Phencyclidine (PCP)-induced deficits of prepulse inhibition in monkeys. Neuroreport 12: 117–120.
- 13. Yeomans JS, Lee J, Yeomans MH, Steidl S, Li L (2006) Midbrain pathways for prepulse inhibition and startle activation in rats. Neuroscience 142: 921–929.
- 14. Fendt M, Koch M, Schinitzler HU (1994) Sensorimotor gating deficit after lesions of the superior colliculus. Neuroreport 5: 1725–1738.
- 15. Cynader M, Berman N (1972) Receptive-field organization of monkey superior colliculus. J Neurophysiol 35: 187–201.
- 16. Robinson DA (1972) Eye movements evoked by collicular stimulation in the alert monkey. Vision Res 12: 1795–1808.
- 17. Sparks DL (1986) Translation of sensory signals into commands for control of saccadic eye movements: role of primate superior colliculus. Physiol Rev 66: 118–171.
- 18. Isa T (2002) Intrinsic processing in the mammalian superior colliculus. Curr Opin Neurobiol 12: 668–677.
- 19. Doubell TP, Skaliora I, Baron J, King AJ (2003) Functional connectivity between the superficial and deeper layers of the superior colliculus: an anatomical substrate for sensorimotor integration. J Neurosci 23: 6596–607.
- 20. Ignashchenkova A, Dicke PW, Haarmeier T, Their P (2004) Neuron specific contribution of the superior colliculus to overt and covert shifts of attention. Nat Neurosci 7: 56–64.
- 21. Coimbra NC, Oliveira R, Freitas RL, Ribeiro SJ, Borelli KG, et al. (2006) Neuroanatomical approaches of the tectum-reticular pathways and immunohistochemical evidence for serotonin-positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensive behavior and fear-induced analgesia. Exp Neurol 197: 93–112.
- 22. Isbell LA (2006) Snakes as agents of evolutionary change in primate brains. J Hum Evol 51: 1–35.
- 23. Maior RS, Hori E, Barros M, Teixeira DS, Tavares MCH, et al. (2011) Superior colliculus lesions impair threat responsiveness in infant capuchin monkeys. Neurosci Lett 504: 257–260.
- 24. Maior RS, Hori E, Uribe CE, Saletti PG, Ono T, et al. (2012) A role for the superior colliculus in the modulation of threat responsiveness in primates: toward the ontogenesis of the social brain. Rev Neurosci 23: 697–706.
- 25. Harting JK, Van Lieshout DP (2000) Projections from the rostral pole of the inferior colliculus to the cat superior colliculus. Brain Res 881: 244–247.
- 26. Stein BE, Magalhães-Castro B, Kruger L (1976) Relationship between visual and tactile representations in cat superior colliculus. J Neurophysiol 39: 410–419.
- 27. Bell AH, Meredith MA, Opstal AJV, Munoz DP (2005) Crossmodal integration in the primate superior colliculus underlying the preparation and initiation of saccadic eye movements. J Neurophysiol 93: 3659–3673.
- 28. Maravita A, Bolognini N, Bricolo E, Marzi CA, Savazzi S (2008) Is audiovisual integration subserved by the superior colliculus in humans? Neuroreport 19: 271–275.
- 29. Manocha SL, Shantha TR, Bourne GH (1968) A stereotaxic atlas of the brain of the Cebus monkey (Cebus apella). Oxford: Clarendon Press. 97 p.
- 30. Linn GS, Negi SS, Gerum SV, Javitt DC (2003) Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys. Psychopharmacology 169: 234–239.
- 31. Fendt M (1999) Enhancement of prepulse inhibition after blockade of GABA activity within the superior colliculus. Brain Res 833: 81–85.
- 32. King AJ, Hutchings ME (1987) Spatial response properties of acoustically responsive neurons in the superior colliculus of the ferret: a map of auditory space. J Neurophysiol 57: 596–624.
- 33. Jay MF, Sparks DL (1987) Sensorimotor integration in the primate superior colliculus. II. Coordinates of auditory signals. J Neurophysiol 57: 35–55.
- 34. Northmore OPM, Levine ES, Schneider GE (1988) Behavior evoked by electrical stimulation of the hamster superior colliculus. Exp Brain Res 73: 595–605.
- 35. Brandão ML, Troncoso AC, de Souza Silva MA, Huston JP (2003) The relevance of neuronal substrates of defense in the midbrain tectum to anxiety and stress: empirical and conceptual considerations. Eur J Pharmacol 463: 225–233.
- 36. Thompson RF (2009) Habituation: a history. Neurobiol Learn Mem 92: 127–134.
- 37. Rankin CH, Abrams T, Barry RJ, Bhatnagar S, Clayton DF, et al. (2009) Habituation revisited: An updated and revised description of the behavioral characteristics of habituation. Neurobiol Learn Mem 92: 135–138.
- 38. Lane ST, Franklin JC, Curran PJ (2013) Clarifying the nature of startle habituation using latent curve modelling. Int J Psychophysiol 88: 55–63.
- 39. Geyer MA, Braff DL (1987) Startle habituation and sensorimotor gating in schizophrenia and related animals. Schizophr Bull 13: 643–668.
- 40. Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psych 49: 206–215.
- 41. Williams LE, Blackford JU, Luksik A, Gauthier I, Heckers S (2013) Reduced habituation in patients with schizophrenia. Schizophr Res 151: 124–132.
- 42. Feifel D, Reza TL, Wustrow DJ, Duff-Davis M (1999) Antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist. J Pharm Exp Ther Novel 288: 710–713.
- 43. Ballmaier M, Bortolato M, Rizzetti C, Zoli M, Gessa G, et al. (2007) Cannabinoid receptor antagonists counteract sensorimotor gating deficits in the phencyclidine model of psychosis. Neuropsychopharmacology 32: 2098–2107.
- 44. Gacśalyi I, Nagy K, Pallagi K, Lévay G, Hársing LG Jr, et al. (2013) Egis-11150: a candidate antipsychotic compound with procognitive eficacy in rodents. Neuropharmacol 64: 254–263.