Intracerebroventricular infusion of the galanin antagonist M40 attenuates heterosexual partner preference in ferrets.

Gonadectomized, estradiol-treated male and female ferrets (Mustela furo) received intracerebroventricular (icv) infusions of 4 doses of the galanin receptor antagonist M40 or galanin and were allowed to approach breeding male or female ferrets that were placed behind wire mesh barriers in the goal boxes of a T maze. After icv infusion of saline, subjects strongly preferred to approach stimulus ferrets of the opposite sex. Male and female subjects approached these preferred stimulus animals on significantly fewer trials after icv infusion of the 2 highest doses of M40, whereas this drug failed to affect males' coital behavior in separate tests with an estrous female. Endogenous galanin may facilitate neural reward mechanisms that control heterosexual partner preference in both sexes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to-position performance in rats lesioned with the cholinergic immunotoxin –2–92IgG-Saporin.

Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's disease (AD) and impairs performance on rodent learning and memory tasks. M40, a peptidergic galanin receptor ligand, blocks galanin-induced impairments on delayed non-matching-to-position (DNMTP). The present experiments used the –2–9–2IgG-saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP when cholinergic transmission was reduced. Hippocampal choline acetyltransferase levels were correlated with DNMTP choice accuracy in lesioned rats. Intracerebroventricular (icv) galanin reduced choice accuracy in both the lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not affect choice accuracy in either group. These results suggest that excess galanin can produce further deficits in DNMTP performance in a lesion model of AD, but blocking endogenous galanin is not sufficient alone to improve performance in lesioned rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis

The rapid membrane actions of glucocorticoid were investigated by intracellular electrical recording from 383 coeliac ganglion neurons of guinea-pig in vitro. Thirty-eight neurons were hyperpolarizaed by 2-12 mV when perfused with 1 mumol/L hydrocortisone 21-hemisuccinate (F-suc), associated with a decrease in input membrane resistance. The hyperpolarization was dose-dependent. Nine neurons were depolarized, and the other 336 neurons were unresponsive. The membrane current was also observed with discontinuous single-electrode voltage clamp technique under perfusion of F-suc in another 43 neurons. In five neurons the current was found outward, but it was inward in one neuron. The hyperpolarization persisted after the elimination of synaptic input by low Ca2+ high Mg2+ perfusion and the suppression of protein synthesis by antinomycin D. The reversal potential of F-suc hyperpolarization is -79 +/- 4.3 mV (n = 5). F-suc induced hyperpolarization and GABA induced depolarization could occur in same neuron. The later action could be blocked by picrotoxin. F-suc induced hyperpolarization could be inhibited by TEA and 4-AP, but not picrotoxin. It is suggested that the F-suc's hyperpoalrization is mediated by potassium channel rather than Cl- channel in the sympathetic ganglion neurons.     

The severity of naloxone-precipitated opiate withdrawal is attenuated by felbamate, a possible glycine antagonist

Recent studies indicate that an N-methyl-D-aspartate (NMDA) receptor system in the rostral medulla is involved in opiate withdrawal. Although NMDA antagonists attenuate naloxone-precipitated opiate withdrawal, they can cause phencyclidine (PCP)like effects that contraindicate clinical use. Because NMDA channels contain sites for the glutamate coagonist, glycine, we assessed the effects of glycinergic agents on naloxone-precipitated opiate withdrawal in rats. The putative antagonist, felbamate (100, 300 mg/kg), attenuated overall withdrawal severity in a dose-related manner and reduced occurrences of chews, teeth chatters, and penile grooming. The partial agonist, D-cycloserine (3, 10 mg/kg), attenuated withdrawal severity, but not in a dose-related manner. Conversely, the low dose of the partial agonist, (+/-)-HA-966 (3, 10 mg/kg), heightened the occurrences of some withdrawal signs. These results support a role for glycine in opiate withdrawal and suggest that these agents, which do not cause PCPlike effects, may be potential treatment for agents for opiate detoxification.     

Normal-phase liquid chromatography-particle-beam mass spectrometry in drug metabolism studies of the dopamine receptor antagonist Odapipam and the muscarine M1 receptor agonist Xanomeline

1. The metabolism of Odapipam has been studied with phenobarbital-induced rat liver microsomes, followed by analysis with normal-phase hplc in combination with particle-beam mass spectrometry. 2. During the incubation of Odapipam, five different metabolites were formed. The EI+ mass spectra of the metabolites indicated the formation of N-desmethyl-Odapipam, 1-hydroxy-Odapipam, the two isomers of 3'-hydroxy-Odapipam and a metabolite which was dehydrogenated in the dihydrobenzofuran moiety. 3. The intrinsic hepatic extraction ratio and metabolism of Xanomeline has been studied in the perfused rat liver. Increasing the input concentration resulted in measurable concentrations of Xanomeline in the perfusate, although the extraction ratio was still > 0.9 at 140 microM. 4. Analysis of the perfusate by normal-phase hplc and particle-beam mass spectrometry showed the formation of at least six metabolites. The EI+ mass spectrum of the metabolites indicated the formation of omega-3 hydroxy-, omega-2 hydroxy-, omega-1 hydroxy-, omega-1 keto-Xanomeline in addition to omega-1 hydroxy-N-desmethyl-Xanomeline and an N-oxide of Xanomeline. 5. The results show that normal-phase hplc based on silica material is superior to reversed-phase-based systems in terms of selectivity. Furthermore, the use of non-aqueous solvents in combination with particle-beam mass spectrometry is advantageous compared with reversed-phase hplc since changing between different solvents in normal-phase hplc results only in minor changes in the particle-beam interface parameters such as nebulizer position, helium pressure and interface temperature.     

Inhibition of sympathetic outflow by the angiotensin II receptor antagonist, eprosartan, but not by losartan, valsartan or irbesartan: relationship to differences in prejunctional angiotensin II receptor blockade

It is well established that angiotensin II can enhance sympathetic nervous system function by activating prejunctional angiotensin II type I (AT1) receptors located on sympathetic nerve terminals. Stimulation of these receptors enhances stimulus-evoked norepinephrine release, leading to increased activation of vascular alpha 1-adrenoceptors and consequently to enhanced vasoconstriction. In the present study, the effects of several chemically distinct nonpeptide angiotensin II receptor antagonists were evaluated on pressor responses evoked by activation of sympathetic outflow through spinal cord stimulation in the pithed rat. Stimulation of thoracolumbar sympathetic outflow in pithed rats produced frequency-dependent pressor responses. Infusion of sub-pressor doses of angiotensin II (40 ng/kg/min) shifted leftward the frequency-response curves for increases in blood pressure, indicating augmented sympathetic outflow. Furthermore, pressor responses resulting in spinal cord stimulation were inhibited by the peptide angiotensin II receptor antagonist, Sar1, Ile8 [angiotensin II] (10 micrograms/kg/min). These results confirm the existence of prejunctional angiotensin II receptors at the vascular neuroeffector junction that facilitate release of norepinephrine. The nonpeptide angiotensin II receptor antagonist, eprosartan (0.3 mg/kg i.v.), inhibited the pressor response induced by spinal cord stimulation in a manner similar to that observed with the peptide antagonist, Sar1, Ile8[angiotensin II]. In contrast, equivalent doses (0.3 mg/kg i.v.) of other nonpeptide angiotensin II receptor antagonists, such as losartan, valsartan, and irbesartan, had no effect on spinal cord stimulation of sympathetic outflow in the pithed rat. Although the mechanism by which eprosartan, but not the other nonpeptide angiotensin II receptor antagonists, inhibits sympathetic outflow in the pithed rat is unknown, one possibility is that eprosartan is a more effective antagonist of prejunctional angiotensin II receptors that augment neurotransmitter release. Because eprosartan is more effective in inhibiting sympathetic nervous system activity compared to other chemically distinct nonpeptide angiotensin II receptor antagonists, eprosartan may be more effective in lowering systolic blood pressure and in treating isolated systolic hypertension.     

Apoptosis induced in neuronal cultures by either the phosphatase inhibitor okadaic acid or the kinase inhibitor staurosporine is attenuated by isoquinolinesulfonamides H-7, H-8, and H-9

OBJECTIVE: The present study evaluated body image assessment and cue reactivity in women with bulimia and controls in response to neutral, mood, and food cues in isolation, and mood and food cues in combination. METHOD: Subjects were 7 women with bulimia nervosa and 8 control women. Food cues were individualized high-risk/favorite foods. Low mood was elicited using the Musical Mood Induction Procedure. Order of cue presentation was random across subjects. Body image and cue reactivity were assessed using a computer version of the silhouette method and self-report ratings, respectively. RESULTS: Women with bulimia consistently rated their current body as being larger and their body image satisfaction as being lower than control women. In addition, women with bulimia differentially rated their current body and a picture of a healthy weight woman as being larger following exposure to food and/or mood cues. Ratings of ideal body were differentially affected by mood cues for control women. Ratings of body satisfaction were not affected by cue presentation. Mere presentation of high-risk foods in the absence of eating was sufficient to elicit urges to binge in women with bulimia. DISCUSSION: Body size estimation is not only affected by enduring characteristics (i.e., bulimia nervosa), but also more transient factors such as short-term exposure to salient food and mood cues.     

Intake of high-fat food is selectively enhanced by mu opioid receptor stimulation within the nucleus accumbens

The present study was designed to further investigate the nature of feeding induced by opioid stimulation of the nucleus accumbens through an examination of the effects of intra-accumbens (ACB) opioids on macronutrient selection. In 3-hr tests of free-feeding (satiated) rats, intra-ACB administration of the mu receptor agonist D-Ala2,N,Me-Phe4, Gly-ol5-enkephalin (DAMGO; 0, 0.025, 0.25 and 2.5 micrograms bilaterally) markedly enhanced the intake of fat or carbohydrate when the diets were presented individually (although the effect on fat intake was much greater in magnitude). Intra-ACB injections of DAMGO, however, produced potent preferential stimulatory effects on fat ingestion with no effect on carbohydrate ingestion when both fat and carbohydrate diets were present simultaneously. Moreover, this selective stimulation of fat intake was independent of base-line diet preference and could be blocked by systemic injection of naltrexone (5 mg/kg). We also examined the effect of 24-hr food deprivation on the pattern of macronutrient intake in rats with access to both carbohydrate and fat. In contrast to the DAMGO-induced selective enhancement of fat intake, food deprivation significantly increased the intake of both diets to the same extent; however, in this case, only the stimulated fat intake was blocked by systemic naltrexone. Intra-ACB administration of DAMGO in hungry rats produced an effect similar to that observed in free-feeding rats; preference was strongly shifted to fat intake. Similarly, the opioid antagonist naltrexone (20 micrograms) infused directly into ACB preferentially decreased fat intake in hungry rats. These findings suggest that endogenous opioids within the ventral striatum may participate in the mechanisms governing preferences for highly palatable foods, especially those rich in fat.     

The antisecretory effects of clozapine, a dopamine D4 receptor antagonist, are blocked by the dopamine D1 receptor antagonist, SCH23390

Dopaminergic compounds affect gastric secretion and response to experimental gastric mucosal injury. We showed previously that the novel dopamine D4 receptor antagonist, clozapine, significantly reduces gastric acid secretion and restraint stress-induced gastric lesions. Because the selectivity of clozapine for D4 receptors has recently been questioned, we tested the ability of a known D1 receptor blocker, SCH23390, to affect clozapine-induced reduction in gastric acid secretion. SCH23390 given i.p. or i.c.v., at doses that did not affect gastric acid secretion, significantly blocked the anti-secretory effect of clozapine, administered either peripherally or centrally. These data suggest that neither clozapine nor SCH23390 exhibit as high a degree of selectivity for the dopamine D4 and D1 receptor, respectively, as previously believed.     

Blockade of radiocontrast-induced nephrotoxicity by the endothelin receptor antagonist, SB 209670

The effect of the novel nonpeptide endothelin (ET) receptor antagonist, (+/-)-SB 209670, on the renal effects of the high osmolar tri-iodinated ionic contrast media, Hypaque, was evaluated in anesthetized dogs in the presence or absence of the cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.v.). Hypaque alone (5 ml/kg, i.v.) resulted in a marked diuresis and natriuresis but little change in either renal blood flow or renal vascular resistance. When the ET receptor antagonist, (+/-)-SB 209670, was infused into the renal artery at a dose that inhibited ET-induced renal vasoconstriction, Hypaque resulted in a significant increase in renal blood flow and decrease in renal vascular resistance. In the presence of indomethacin, Hypaque caused a significant increase in renal vascular resistance which was abolished by (+/-)-SB 209670. The data indicate that the radiocontrast media, Hypaque, can cause renal vasoconstriction which may be mediated by ET.     

Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid

Vitamin A is required for reproduction and normal embryonic development. We have determined that all-trans-retinoic acid (atRA) can support development of the mammalian embryo to parturition in vitamin A-deficient (VAD) rats. At embryonic day (E) 0.5, VAD dams were fed purified diets containing either 12 micrograms of atRA per g of diet (230 micrograms per rat per day) or 250 micrograms of atRA per g of diet (4.5 mg per rat per day) or were fed the purified diet supplemented with a source of retinol (100 units of retinyl palmitate per day). An additional group was fed both 250 micrograms of atRA per g of diet in combination with retinyl palmitate. Embryonic survival to E12.5 was similar for all groups. However, embryonic development in the group fed 12 micrograms of atRA per g of diet was grossly abnormal. The most notable defects were in the region of the hindbrain, which included a loss of posterior cranial nerves (IX, X, XI, and XII) and postotic pharyngeal arches as well as the presence of ectopic otic vesicles and a swollen anterior cardinal vein. All embryonic abnormalities at E12.5 were prevented by feeding pharmacological amounts of atRA (250 micrograms/g diet) or by supplementation with retinyl palmitate. Embryos from VAD dams receiving 12 micrograms of atRA per g of diet were resorbed by E18.5, whereas those in the group fed 250 micrograms of atRA per g of diet survived to parturition but died shortly thereafter. Equivalent results were obtained by using commercial grade atRA or atRA that had been purified to eliminate any potential contamination by neutral retinoids, such as retinol. Thus, 250 micrograms of atRA per g of diet fed to VAD dams (approximately 4.5 mg per rat per day) can prevent the death of embryos at midgestation and prevents the early embryonic abnormalities that arise when VAD dams are fed insufficient amounts of atRA.     

Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli

ST2/T1 is an orphan receptor highly homologous to the IL-1 receptor. Using ST2 cDNA, ST2 specific primers, and a polyclonal antibody generated against ST2, the expression of mRNA and protein corresponding to both the soluble and membrane anchored forms of ST2 was studied. ST2 mRNAs were ubiquitously expressed in all the human tissues examined and were induced by cytokines and phorbol esters. Three different species of mRNAs were observed in different human cells and tissues. In contrast, only two species of ST2 mRNAs were observed in murine Balb/c-3T3 cells and no ST2 mRNA was seen in most tissues of normal mice. However, in a murine model where mouse ears are exposed to UVB irradiation leading to inflammation, ST2 mRNA was expressed 48 h post UV exposure. Similarly, in Balb/c-3T3 cells, the expression of soluble ST2 mRNA and protein was induced by pro-inflammatory stimuli such as TNF, IL-1alpha, IL-1beta and PMA in both exponentially growing and quiescent cells. The expression of the membrane ST2, however, remained constant. These data suggest a role for ST2 in inflammation.     

Spatial localization in the Morris water maze in rats: Acquisition is affected by intra-accumbens injections of the dopaminergic antagonist haloperidol.

Previous studies (e.g., G. E. Ploeger et al; see record 1993-20962-001) showed that low doses of systemically injected haloperidol affected spatial learning in the Morris water maze. This study investigated effects of intra-accumbens injections of haloperidol on spatial learning. To control for motivation and sensorimotor coordination, the researchers trained rats to escape onto a visible platform. Low doses (50–200 ng) of haloperidol impaired spatial learning, whereas escaping on a visible platform was undisturbed. The 500-ng dose of haloperidol completely blocked acquisition because of combined learning and motor impairments. Retrieval of an acquired escape response was unaffected by 500 ng haloperidol. The data show that mesolimbic dopaminergic activity is involved in the acquisition of spatial localization. The results are related to studies demonstrating the involvement of the nucleus accumbens in cue-directed behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala.

24 female rats, with chronic cannula placed bilaterally in the amygdala, received infusions of the N-methyl-{d}-aspartate (NMDA) receptor antagonist {d},{l}-2-amino-5-phosphonovaleric acid (APV) before contextual Pavlovian fear conditioning. Administration of APV to the basolateral nucleus prevented acquisition of fear. Central nucleus infusions had no effect. It is concluded that an NMDA-mediated process near the basolateral region of the amygdala (e.g., lateral or basolateral nucleus) is essential for the learning of fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GR144053, a fibrinogen receptor antagonist, enhances the suppression of neointima formation by losartan, an angiotensin II receptor antagonist, in the injured carotid artery of hamster

1. The present study investigated the inhibitory effect of losartan, a type 1 angiotensin II (AT1) antagonist, and of combined treatment with losartan and GR144053, a fibrinogen receptor (GPIIb/IIIa) antagonist, on neointima formation subsequent to vascular injury in the hamster carotid artery. Vascular injury was achieved by a roughened-tip 2F catheter and the neointimal area was measured up to 2 weeks inducing the injury. 2. Compared to non-treated hamsters (intimal area (IA/internal elastic laminal area (IELA) ratio = 60.3 +/- 5.9%, n = 12), losartan dissolved in drinking water (1, 3 and 10 mg kg-1 per day, n = 8 each) reduced neointimal area dose-dependently, a significant decrease (IA/IELA = 39.7 +/- 5.6%) being attained with the highest dose when it was administered from 1 day before injury. However, neointima formation was not prevented even with the highest dose of losartan when the administration was started after injury. 3. When the administration of GR144053 (1.0 mg kg-1 per hour) via an implanted osmotic pump was started 30 min before the injury and continued for the next 2 weeks, no suppression of neointima formation was observed, although platelet aggregation evoked ex vivo by adenosine diphosphate (ADP) at the end of treatment period was efficiently inhibited. 4. In separate experiments in which 5-bromo-2-deoxy-Uridine (BrdU) was used to test smooth muscle cell (SMC) proliferation 1 and 7 days after injury, the ratio of SMC proliferation in the injured area was only slightly decreased by losartan when its administration was started after the injury, despite the marked reduction of SMC proliferation when treatment was started before the injury. Treatment with GR144053 as indicated above also significantly decreased the SMC proliferating index 1 day after the injury. 5. To examine the potential benefit of the coadministration of the GPIIb/IIIa antagonist with the AT1 receptor antagonist, GR144053 (1.0 mg kg-1 per hour) was combined with post-injury treatment with losartan (10 mg kg-1 per day). This markedly reduced the proliferation of SMCs and significantly decreased the neointimal area (IA/IELA = 31.2 +/- 4.6%) measured 2 weeks following the catheterization. 6. According to the results of a time-dependent study in which GR144053 was given in combination with post injury treatment with losartan for 1, 3, 7 or 14 days, neointima formation could be reduced by treatment with GR144053 for just 7 days. 7. In conclusion, GR144053, a fibrinogen receptor antagonist, enhanced the inhibitory effect of losartan, an AT1 receptor antagonist, on neointima formation in the damaged carotid artery of hamsters.     

Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A

This study examined the effect of the cannabinoid receptor agonist, WIN 55212-2, on the electrically evoked release of [14C]acetylcholine (ACh) from superfused brain slices from the hippocampus, a region with a high density of cannabinoid receptors. A comparison was also made with [14C]ACh release from the nucleus accumbens, which has relatively fewer cannabinoid receptors. In the hippocampal slices, WIN 55212-2 produced a dose-dependent inhibition of [14C]ACh release, with an EC50 of 0.03 microM and a maximal inhibition of 81% at 1 microM. In the nucleus accumbens slices, WIN 55212-2 produced a weak inhibition of [14C]ACh release, which did not quite reach statistical significance. The inhibition of electrically evoked hippocampal [14C]ACh release by WIN 55212-2 could be prevented by the cannabinoid receptor antagonist, SR 141716A (EC50, 0.3-1.0 microM). In addition to antagonizing the effects of WIN 55212-2, SR 141716A alone produced a 2-fold potentiation of the electrically stimulated [14C]ACh release in this region (EC50, 0.1-0.3 microM). By contrast, in nucleus accumbens slices, no potentiation of the stimulated release of [14C]ACh release by SR 141716A was observed. Basal [14C]ACh release was unaffected by WIN 55212-2 or SR 141716A in either area. These results suggest that cannabinoid receptor activation can produce a strong inhibition of ACh release in the hippocampus. Furthermore, the potentiation of ACh release in the hippocampus by SR 141716A alone suggests either that this compound is an inverse agonist at cannabinoid receptors or it is antagonizing the actions of an endogenous ligand acting on these receptors.     

Excitatory amino acid receptor antagonists block the cardiovascular and anxiety responses elicited by gamma-aminobutyric acidA receptor blockade in the basolateral amygdala of rats

Blockade of gamma-aminobutyric acid (GABAA) receptors in the anterior basolateral amygdala (BLA) with bicuculline methiodide results in an increase in heart rate, blood pressure and "anxiety" in rats. Glutamate receptors in the BLA are also reported to be involved in eliciting anxiety responses. The purpose of this study was to investigate the interaction between GABAergic inhibition and glutamatergic excitation in the BLA. Male Wistar rts were implanted with femoral arterial catheters and bilateral chronic microinjection cannulae into the BLA. Each animal was injected with either artificial cerebrospinal fluid (100 nl), bicuculline methiodide (10 pmol/100 nl) or bicuculline methiodide + one dose of an antagonist of either the N-methyl-D-aspartate receptor [AP5 (20 and 100 pmol) and dizocilpine (25 and 125 pmol)] or the non-N-methyl-D-aspartate ionotropic receptor [CNQX (10 and 50 pmol) and GYKI 52466 (50 and 250 pmol)]. Increases in heart rate, blood pressure and "anxiety" (as measured in the social interaction test) observed in rats after bicuculline methiodide injections into the BLA were blocked in a dose dependent manner with the concurrent injections of either N-methyl-D-aspartate or non-N-methyl-D-aspartate antagonists, suggesting that activation of both subtypes of glutamate ionotropic receptors may be necessary for the responses elicited by GABAA receptor blockade in the basolateral amygdala.     

The modulation of fragile X behaviors by the muscarinic M4 antagonist, tropicamide.

Muscarinic acetylcholine receptors (mAChR) are G protein–coupled receptors (M1–M5), grouped together into two functional classes, based on their G protein interaction. Although ubiquitously expressed in the CNS, the M4 protein shows highest expression in the neostriatum, cortex, and hippocampus. Electrophysiological and biochemical studies have provided evidence for overactive mAChR signaling in the fragile X knock-out (Fmr1KO) mouse model, and this has been hypothesized to contribute to the phenotypes seen in Fmr1KO mice. To address this hypothesis we used an M4 antagonist, tropicamide, to reduce the activity through the M4 mAChR and investigated the behavioral response in the Fmr1KO animals. Data from the marble-burying assay have shown that tropicamide treatment resulted in a decreased number of marbles buried in the wild-type (WT) and in the knockout (KO) animals. Results from the open field assay indicated that tropicamide increases activity in both the WT and KO mice. In the passive avoidance assay, tropicamide treatment resulted in the improvement of performance in both the WT and the KO animals at the lower doses (2 and 5 mg/kg), and the drug was shown to be important for the acquisition and not the consolidation process. Lastly, we observed that tropicamide causes a significant decrease in the percentage of audiogenic seizures in the Fmr1KO animals. These results suggest that pharmacological antagonism of the M4 receptor modulates select behavioral responses in the Fmr1KO mice. (PsycINFO Database Record (c) 2011 APA, all rights reserved)