[Functional Responses to the Chronic Activation of 5-HT1A Receptors in Mice with Genetic Predisposition to Catalepsy].

The effects of chronic 5-HT1A receptor activation on the behavior, functional activity of 5-HT1A receptors, and expression of key genes of the brain 5-HT system were studied in mice of the catalepsy-prone CBA strain and the catalepsy-resistant C57BL/6 strain. Chronic treatment with 8-Hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) led to a significant decrease in the hypothermic response to acute administration of 8-OH-DPAT in CBA and C57BL/6 mice, which indicates the desensiti-zation of 5-HT1A receptors in both strains. Pretreatment with the 5-HT7 receptor agonist SB 269970 did not affect the hypothermic response to the acute administration of 8-OH-DPAT, which suggests an independent functional response of 5-HT1A receptors. The treatment did not induce any changes in the behavior in the open field paradigm in CBA mice, but significantly increased the total path, the time spent in the center, and the number of rearings in C57BL/6 mice, which indicates the enhancement of locomotor and exploratory activity in C57BL/6 mice. The chronic activation of 5-HT1A receptor downregulated 5-HT1A gene expression, as well as the expression of the gene that encodes tryptophan hydroxylase 2, a key enzyme of 5-HT biosynthesis, in the midbrain and the expression of the gene that encodes the 5-HT2A receptor in the frontal cortex of CBA, but not C57BL/6 mice. The obtained data provide a new evidence on the receptor-gene cross talk in the brain 5-HT system that may underlie the loss of pharmacological efficacy of 5-HT1A receptor agonists. In turn, the loss of the behavioral response and compensatory alterations in key genes of the brain 5-HT system in CBA mice suggests that catalepsy-prone and -resistant genotypes demonstrate different sensibility to the effects of drugs.

The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo.

G protein-coupled receptor 37 (GPR37) is an orphan receptor associated to Parkinson's disease (PD) neuropathology. Here, we identified GPR37 as an inhibitor of adenosine A2A receptor (A2AR) cell surface expression and function in vivo. In addition, we showed that GPR37 and A2AR do oligomerize in the striatum. Thus, a close proximity of GPR37 and A2AR at the postsynaptic level of striatal synapses was observed by double-labelling post-embedding immunogold detection. Indeed, the direct receptor-receptor interaction was further substantiated by proximity ligation in situ assay. Interestingly, GPR37 deletion promoted striatal A2AR cell surface expression that correlated well with an increased A2AR agonist-mediated cAMP accumulation, both in primary striatal neurons and nerve terminals. Furthermore, GPR37-/- mice showed enhanced A2AR agonist-induced catalepsy and an increased response to A2AR antagonist-mediated locomotor activity. Overall, these results revealed a key role for GPR37 controlling A2AR biology in the striatum, which may be relevant for PD management.

Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.

Alteration of the brain morphology and the response to the acute stress in the recombinant mouse lines with different predisposition to catalepsy.

Catalepsy is an inability to correct an externally imposed awkward posture; it is associated with schizophrenia and depression in human. We created new recombinant B6.CBA-D13Mit76C and B6.CBA-D13Mit76B mouse lines on the C57Bl/6 genome, carrying the 102.73-110.56Mbp fragment of chromosome 13 derived from the catalepsy-prone CBA strain and catalepsy-resistant C57BL/6 strain, respectively. We compared the behavior and brain morphology (11.7T BioSpec 117/16 USR tomograph, Germany) in these lines. The effects of acute emotional stress on corticosterone's level in the blood and mRNA expression of Bdnf and Arc genes in the brain were investigated. The B6.CBA-D13Mit76B mice were non-cataleptic, while about 17% of B6.CBA-D13Mit76C mice demonstrated catalepsy-like immobility. No difference between these lines was revealed in the open field and social interaction tests. In the Morris water maze test, both lines effectively found the platform on the fourth day; however B6.CBA-D13Mit76B mice achieved significantly better results than cataleptic-prone animals. B6.CBA-D13Mit76C mice were characterized by decreased volume of the total brain and reduced sizes of striatum, cerebellum and pituitary gland. The both lines showed the similar basal and stress-induced levels of corticosterone, while the brain expression of Bdnf and Arc genes was more vulnerable to stress in the catalepsy-prone B6.CBA-D13Mit76C line.

Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease).

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death.

Alterations in pharmacological and behavioural responses in recombinant mouse line with an increased predisposition to catalepsy: role of the 5-HT1A receptor.

BACKGROUND AND PURPOSE: One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties. EXPERIMENTAL APPROACH: Two mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT1A receptor were compared. KEY RESULTS: B6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT1A receptor agonist 8-OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT1A receptor-mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT1A receptor. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that transfer of the main locus of hereditary catalepsy containing the 5-HT1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT1A receptor-related drugs specifically acting on either pre- or postsynaptic receptors. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

[STUDY CATALEPSY AND OTHER FORMS OF BEHAVIOR WITH RECOMBINANT MICE].

Catalepsy--passive defense freezing reaction in response to the threatening stimuli. In hypertrophic form, it is a symptom of brain dysfunction. In mice, the major gene that determines predisposition to catalepsy localized in the distal fragment 111.35-116.16 m. p. n. of chromosome 13. This chromosome fragment using backcrossing was transferred from the cataleptic CBA mouse stain to the genome of catalepsy resistant mouse strain C57BL/6. It was obtained two recombinant lines C57BL6.CBA-Dl3Mit76C and C57BL6.CBA-D13Mit76B, carrying the fragment of CBA and C57BL/6, respectively. It has been shown that in C57BL6.CBA-D13Mit76C mice the number of cataleptic higher compared with the control line C57BL6.CBA-Dl3Mit76B. In tests "startle reflex reaction" and "social interaction" differences in behavior were not found. At the same time reduction of exploratory behavior in the "open field" test of C57BL6.CBA-D13Mit76C mice compared with C57BL6.CBA-D13Mit76B mice was shown. Immobility time of C57BL6.CBA-D13Mit76C mice in the "forced swimming" test was also significantly lower compared to control mice C57BL6.CBA-D13Mit76B.

[Comparison of behavioral effects of fluoxetine, imipramine and new psychotropic drug TC-2153 on mice with hereditary predisposition to catalepsy].

Behavioral effects of classic antidepressants, fluoxetine and imipramine, and new psychotropic benzopentathiepin TC-2153 (20 mg/kg, per os) were studied on mice differing in the predisposition to catalepsy-noncataleptic AKR strain and cataleptic strains CBA and AKR.CBA-D13Mit76 (D13). Mice of D13 strain was created by transferring the CBA-allele of major locus of catalepsy to AKR genome. In the forced swim test (FST) fluoxetine showed antidepressant effect on mice of all three strains, imipramine was effective only in D13 mice, while TC-2153 produced antidepressant effect on AKR and D13 mice. Unlike to imipramine and fluoxetine, TC-2153 did not produce negative side effects in the open field and elevated plus-maze tests. Thus, TC-2153 produces antidepressant effects similar to imipramine and fluoxetine, without any visible negative side effect on locomotory activity and anxiety. The D13 mice in the FST showed high sensitivity to the studied drugs in comparison to the parent strains and can be used as new genetic model for investigation of the mechanism of antidepressant effects.

An adaptive role of TNFα in the regulation of striatal synapses.

Elevation of inflammatory cytokines in the striatum precedes symptoms in a number of motor dysfunctions, but it is unclear whether this is part of the disease process or an adaptive response to the pathology. In pyramidal cells, TNFα drives the insertion of AMPA-type glutamate receptors into synapses, and contributes to the homeostatic regulation of circuit activity in the developing neocortex. Here we demonstrate that in the mouse dorsolateral striatum, TNFα drives the internalization of AMPARs and reduces corticostriatal synaptic strength, dephosphorylates DARPP-32 and GluA1, and results in a preferential removal of Ca(2+)-permeable AMPARs. Striatal TNFα signaling appears to be adaptive in nature, as TNFα is upregulated in response to the prolonged blockade of D2 dopamine receptors and is necessary to reduce the expression of extrapyramidal symptoms induced by chronic haloperidol treatment. These data indicate that TNFα is a regulator of glutamatergic synaptic strength in the adult striatum in a manner distinct from its regulation of synapses on pyramidal cells and mediates an adaptive response during pathological conditions.

Spatial learning in the Morris water maze in mice genetically different in the predisposition to catalepsy: the effect of intraventricular treatment with brain-derived neurotrophic factor.

Hereditary catalepsy in mice is accompanied with volume reduction of some brain structures and high vulnerability to inflammatory agents. Here an association between hereditary catalepsy and spatial learning deficit in the Morris water maze (MWM) in adult mouse males of catalepsy-resistant AKR, catalepsy-prone CBA and AKR.CBA-D13Mit76 (D13) strains was studied. Recombinant D13 strain was created by means of the transfer of the CBA-derived allele of the major gene of catalepsy to the AKR genome. D13 mice showed a low MWM performance in the acquisition test and high expression of the gene coding proinflammatory interleukin-6 (Il-6) in the hippocampus and cortex compared with mice of the parental AKR and CBA strains. An acute ivc administration of 300 ng of brain derived neurotrophic factor (BDNF) normalized the performance in the MWM, but did not decrease the high Il-6 gene expression in the brain of D13 mice. These results indicated a possible association between the hereditary catalepsy, MWM performance, BDNF and level of Il-6 mRNA in the brain, although the relation between these characteristics seems to be more complex. D13 recombinant mice with deficit of spatial learning is a promising model for study of the genetic and molecular mechanisms of learning disorders as well as for screening potential cognitive enhancers.

[Coexpression of genes located in the 111.35-116.16 Mb of chromosome 13 in mice with different predisposition to catalepsy].

Catalepsy is a pathologic behavior which is usually associated with a dysfunction of striatal pallidal pathway and which can be caused by different mechanisms. It was showned previously that hereditary catalepsy is linked with the distal 111.35-116.16 Mb of chromosome 13. We investigated the level of mRNA of 42 genes located in this fragment in two brain regions which are concerned with catalepsy-striatum and substantia nigra in catalepsy-resistant AKR mice strain, in cataleptic CBA mice strain and in congenic cataleptic AKR.CBA-D13Mit76 (D13) mice strain which were created by transferring of this fragment from CBA in AKR genome. We showed congenic D13 mice vary from AKR in level of mRNA of 2 genes (Ndufs4 and Ppap2a genes) in striatum and 10 genes (Esm1, Fst, Gm10735, Gm15322, Gm15323, Gm15324, Gm15325, Il6st, II31ra, Itga1) in sibstantia nigra. The level of mRNA of Mcidas gene is reduced in both brain regions in D13 compared to AKR. Gene expression of Hspb3 n Mocs2, which codes heat shock protein and, molybdenum cofactor synthesis, respectively, in substantia nigra is reduced in cataleptic CBA and D13 mice compared to catalepsy-resistant AKR mice. These genes can be considered as the most likely genes candidate of catalepsy. The revealed genes coexpression shows that there is a difficult genes network, which regulates hereditary catalepsy.

[Serotonin and dopamine brain metabolism in mice with different predisposition to catalepsy].

Catalepsy usually is caused by imbalance of dopamine (DA) and serotonin (5-HT) systems of brain. The aim of our work was to verify if this imbalance plays an important role in the mechanism of hereditary catalepsy in mice. Maintenance of DA, 5-HT and their main metabolites--5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, homovanilic acid was determined in cortex, hypothalamus, hippocampus, striatum, substantia nigra and nuclei raphes in catalepsy-resistant AKR/J mice strain and catalepsy-prone CBA/LacJ mice strain and recombinant mice AKR/J.CBA-D13Mit76 (D13) strain. The latest strain was selected by transferring of a fragment of the chromosome 13 from CBA/LacJ carrying the main gene of hereditary catalepsy to AKR/J genome. There were no interstrain differences in concentration of biogenic amines and their metabolites in all brain regions. As a result of our work the hypothesis about the important role of 5-HT and/or DA systems of brain in the mechanism of hereditary catalepsy in mice was denied.

Comparative phenotypic and cytochemical characteristics of lymphocytes of Wistar rats and rats with genetic predisposition to catalepsy after retabolil administration.

We studied the possibility of using anabolic steroid retabolil injections for complex correction of behavioral and immune parameters in rats with genetic predisposition to catalepsy. Subpopulation composition of lymphoid organ and blood cells was compared in rats with genetic predisposition to catalepsy and Wistar rats after retabolil administration. In rats predisposed to catalepsy, retabolil reduced the total content of thymus cells and increased absolute count of CD8 (+) thymocytes. In Wistar rats, retabolil increased the total cell count and the content of CD4 (+) thymocytes, but reduced the number of CD8 (+) cells. Therefore, changes in the subpopulation composition of thymus cells after retabolil administration were opposite in rats with genetic predisposition to catalepsy and Wistar rats. Retabolil injections reduced the severity of catalepsy response in rats with genetic predisposition. However, the time of freezing in Wistar rats significantly increased under these conditions.

On the association between lipopolysaccharide induced catalepsy and serotonin metabolism in the brain of mice genetically different in the predisposition to catalepsy.

The study of the interaction between nervous and immune systems in the mechanism of psychopathology is an important problem of neuroscience. Catalepsy (freezing reaction) is a passive defensive strategy in response to threatening stimuli. An exaggerated form of catalepsy is a syndrome of some grave mental disorders. Both the brain serotonin (5-HT) and immune systems were shown to be involved in the mechanism of catalepsy. Here we compared the effects of two doses (50 or 200 µg/kg, ip) of innate immune system activator, bacterial lipopolysaccharide (LPS), on catalepsy, 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the hippocampus, striatum, and midbrain of mice of catalepsy-prone (CBA/Lac and AKR.CBA-D13Mit76) and catalepsy-resistant (AKR/J) strains. The expression of LPS-induced catalepsy as well as 5-HIAA/5-HT ratio in the midbrain and striatum were significantly higher in mice of the catalepsy-prone strains compared with animals of the catalepsy-resistant strains. These results indicated an involvement of the brain 5-HT system in the cataleptogenic effect of LPS and open up new vistas for understanding the nervous-immune mechanism of behavioral disorders.

[Il6st gene mRNA and gp130 protein distribution in the brain structures in mice differing in exagerrated freezing reaction (catalepsy)].

Glycoprotein gp130 is involved in the intracellular transduction of signals from receptors ofinterleukin-6--related cytokines. The linkage between Il6st gene encoding gp130 and predisposition to excessive freezing (catalepsy) in mice was shown. The aim of present study was to investigate the Il6st mRNA concentration, the level and the rate of glycosilation of gp130 in five brain structures in catalepsy-resistant AKR/J mice strain and in catalepsy-prone CBA/LacJ, AKR.CBA-D13Mit76 with the CBA-derived Il6st gene variant in the AKR/J genome, and ASC created by selection of back-crosses between CBA and AKR strains on catalepsy. Highest concentrations of the nonglycosilated and the glycosilated gp130 protein levels were detected in the midbrain. High levels of Il6st mRNA were discovered in the midbrain, the striatum and the hypothalamus in all mouse strains. The level of Il6st mRNA in the striatum of AKR.CBA-D13Mit76 mice was significantly higher compared with AKR/J. An association between hereditary catalepsy and Il6st expression in the striatum in mice was suggested.

Pharmacological and genetic evidence for pre- and postsynaptic D2 receptor involvement in motor responses to nociceptin/orphanin FQ receptor ligands.

A combined pharmacological and genetic approach was undertaken to investigate the contribution of endogenous dopamine to the motor actions of nociceptin/orphanin FQ (N/OFQ) receptor (NOP receptor) ligands. Motor activity was evaluated by a battery of behavioural tests in mice. The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/D3 (raclopride, amisulpride) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice. Low doses of N/OFQ and NOP receptor antagonists promoted movement whereas higher doses inhibited it. Motor facilitation was selectively prevented by raclopride while motor inhibition was prevented by amisulpride. Amisulpride also attenuated the hypolocomotion induced by the D2/D3 receptor agonist pramipexole and dopamine precursor l-3,4-dihydroxyphenylalanine, whereas raclopride (and S33084) worsened it. To dissect out the contribution of pre- and postsynaptic D2 receptors, mice lacking the D2 receptor (D2R(-/-)) or its long isoform (D2L(-/-)) were used. Motor facilitation induced by N/OFQ and NOP receptor antagonists was lost in D2R(-/-) and D2L(-/-) mice whereas motor inhibition induced by NOP receptor antagonists (and pramipexole) was lost in D2R(-/-) but preserved in D2L(-/-) mice. N/OFQ-induced hypolocomotion was observed in both genotypes. We demonstrate that motor actions of NOP receptor ligands rely on the modulation of endogenous dopamine. Motor facilitation induced by NOP receptor antagonists as well as low dose N/OFQ is mediated through D2L postsynaptic receptors whereas motor inhibition observed with higher doses of N/OFQ occurs by direct inhibition of mesencephalic DA neurons. Motor inhibition seen with high doses of NOP receptor antagonists appears to be mediated through the D2 presynaptic autoreceptors. These data confirm that endogenous N/OFQ is a powerful modulator of dopamine transmission in vivo and that the effects of NOP receptor antagonists on motor function reflect the blockade of this endogenous N/OFQ tone.

Differential network analysis reveals genetic effects on catalepsy modules.

We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.

Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response.

Catalepsy is a passive defensive strategy in response to threatening stimuli. In exaggerated forms it is associated with brain dysfunctions. The study was aimed to examine (1) possible association of the hereditary catalepsy with neuroanatomical characteristics and (2) sensitivity of the catalepsy expression, HPA and brain serotonin (5-HT) systems to restraint stress (for one hour) in mice of catalepsy-prone (CBA/Lac, ASC (Antidepressant Sensitive Catalepsy), congenic AKR.CBA-D13M76) and catalepsy-resistant (AKR/J) strains. Magnetic resonance imaging showed that the catalepsy-prone mice were characterized by the smaller size of the pituitary gland and the larger size of the thalamus. In ASC mice, diencephalon region (including hypothalamus) and striatum were significantly reduced in size. Restraint stress provoked catalepsy in AKR mice and enhanced it in the catalepsy-prone mice. Stress-induced corticosterone elevation was diminished, while 5-HT metabolism (5-HIAA level or 5-HIAA/5-HT ratio) in the midbrain was significantly augmented by stress in the catalepsy-prone mice. The multivariate factor analysis revealed interactions between the basal levels and the stress-induced alterations of 5-HT metabolism in the hippocampus and midbrain suggesting the interaction between multiple alterations in 5-HT neurotransmission in several brain structures in the regulation of hereditary catalepsy. The study indicated an association between the hereditary catalepsy, neuroanatomical characteristics, and neurochemical responses to emotional stress. The catalepsy-prone genotypes seem to be more susceptible to stress that suggests them as the adequate models to study the genetic predisposition to stress-based neuropathology. The data support the association of hereditary catalepsy with the inherited brain dysfunction of a neurodegenerative nature.

[Effect of GDNF on the behavior of ASC mice with high hereditary predisposition to catalepsy].

ASC mice, which were selected for high predisposition to catalepsy, are convenient genetic model for research of central mechanisms related to disorder of motor regulation. The aim of the work was to study the effect of glial cell line-derived neurotrophic factor (GDNF) on catalepsy, locomotor activity, stereotyping behavior in the marble burying test and on the dopamine level in striatum of ASC mice. It was shown that GDNF increased the locomotor activity in the open field, reduced catalepsy expression and stimulated the stereotyping obsessive-compulsive behavior. These changes in behavior were accompanied by increasing dopamine level in striatum.

Different effects of α- and γ-glycine on the aberrant activity of pyramidal neurons of hippocampal slices.

Experiments in vitro on hippocampal slices of mouse have shown that solutions prepared from polymorphic modifications α- and γ-glycine have different effect on the aberrant activity of neurons. In the presence of α-glycine the excitability of these neurons decreased more slowly, prolonging its modulating effect on NMDA type glutamate receptors. This effect agrees with higher biological activity of α-polymorphic modifications (as compared with that of the α-form) that previously observed with respect to behavior of mice from the line with genetic diathesis to catalepsy, which were used as a biological model for investigation of some pathological behavior forms.