Involvement of Presynaptic 5-HT<Subscript>1A</Subscript> Receptors in Immunomodulation in Conditions of Psychoemotional Tension

The development of an immune reaction in CBA mice during activation and blockade of serotonin 1A (5-HT_1A) autoreceptors with highly selective agents has characteristic features depending on the behavioral stereotype formed. The 5-HT_1A receptor agonist 8-OH-DPAT (0.1 mg/kg 15 min before immunization) did not alter the number of IgM antibody-forming cells in the spleen at the peak of the immune reaction (day 4) in aggressive mice, but increased the number in submissive mice, in which the immune response without treatment was lower than that in aggressive animals. Blockade of the same receptor type with WAY-100635 (0.1 mg/kg 30 min before immunization) led to a decrease in the immune response in animals with aggressive behavior and an increase in submissive animals. The question of the influences of agents acting on presynaptic 5-HT_1A somatodendritic autoreceptors on the immune response, depending on the functional state of 5-HT_1A receptors and the balance of activities in the serotoninergic and dopaminergic systems as a whole, is discussed.     

The Role of Serotonin Receptors in Delta-Opioid Immunosuppression

Studies in CBA mice and Wistar rats demonstrated the involvement of serotonin (5-HT) receptors in immunosuppression evoked using the selective δ2 opioid receptor (δ2-OR) agonist DSLET (100 μg/kg). This opioid effect was seen in conditions of selective activation of 5-HT_1A autoreceptors with 8-OH-DPAT (0.1 mg/kg) and in conditions of prior blockade of postsynaptic 5-HT_1A and 5-HT_2A receptors with WAY-100635 and ketanserin (1 and 3 mg/kg). The question of the different contributions of these types of 5-HT receptor to δ-induced suppression of the immune response is discussed.     

The contribution of serotonin 1A receptors to kappa opioid immunosuppression

Activation of kappa opioid receptors (kappa-OR) with the selective agonist rimorphin (0.1 mg/kg) produced marked suppression of the immune response in CBA mice. This effect was not seen on administration of rimorphin on the background of a reduction in the activity of the serotoninergic (5-HTergic) system resulting from stimulation of presynaptic (8-OH-DPAT, 0.1 mg/kg) or blockade of postsynaptic (WAY-100635, 1.0 mg/kg) 5-HT_1A receptors. These data led to the conclusion that 5-HTergic mechanisms involving preand postsynaptic 5-HT_1A receptors have a role in kappa-opioid-mediated immunosuppression. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 7, pp. 807–813, July, 2008.     

Contribution of 5-HT1A serotonin receptors of the brain to the regulation of hereditary catalepsy

Selective agonists 5-HT_1A of serotonin receptors (8-OH-DPAT and flezinoxan) had an inhibitory effect on the manifestation of hereditary catalepsy in mice and rats. No differences were revealed in specific binding of³H-8-OH-DPAT to 5-HT_1A receptors in the striatum of either cataleptic or noncataleptic mice and rats. Nonetheless, an increase of the density of these receptors was observed in the frontal cortex of CBA mice predisposed to catalepsy in comparison with mice of the noncataleptic C57Bl strain. The data indicate a contribution of 5-HT_1A receptors to the regulation of hereditary catalepsy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 633–635, December, 1994 Presented by V. P. Kaznacheev, Member of the Russian Academy of Medical Sciences     

Involvement of brain serotonin 5-HT<Subscript>1A</Subscript> receptors in genetic predisposition to aggressive behavior

Experiments were performed on Norwegian rats selected over more than 59 generations for high and low levels of high-affective defensive aggressivity and on highly aggressive (offensive) Tg8 mice with irreversible monoamine oxidase A knockout. There were significant differences in the functional state and expression of 5-HT_1A receptors between highly aggressive and non-aggressive animals. Functional activity assessed in terms of hypothermia evoked by a 5-HT_1A agonist was significantly greater in non-aggressive rats and mice than in aggressive animals. The high level of functional activity in non-aggressive rats coincided with a greater level of expression of 5-HT_1A receptors in the midbrain. The level of 5-HT^1A receptor mRNA in aggressive mice was unchanged in the midbrain and hypothalamus and was increased in the frontal cortex and amygdaloid complex. These results led to the conclusion that 5-HT_1A receptors play a significant role in the mechanisms of genetic predisposition to aggressive behavior. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 4, pp. 537–542, July–August, 2006.     

Effect of serotonin 5-HT1A receptor agonists on sexual motivation of male mice

The effect of selective agonists of serotonin 5-HT_1A receptors on sexual arousal (its behavioral and hormonal components) in male CBA mice caused by estral females was studied. Injections of 8-OH-DPAT, flesinoxane, and ipsapirone significantly decreased the main behavioral parameter of sexual motivation (duration of the male's stay near the wall separating it from the receptive female). The activating effect of the female on the pituitary gonadal system of the male was completely blocked: the blood testosterone level did not increase. Therefore, the behavioral and hormonal components of sexual activation of males are regulated by the serotonin mechanisms alone, in which the cerebral 5-HT_1A receptors are involved. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 224–226, February, 1999     

Receptor-genes cross-talk: effect of chronic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin treatment on the expression of key genes in brain serotonin system and on behavior

Dysfunction in brain serotonin (5-HT) system has been implicated in the psychopathology of anxiety, depression, drug addiction, and schizophrenia. The 5-HT_1A receptors play a central role in the control of 5-HTergic neurotransmission. There are some scarce data showing cross-regulation between 5-HT receptors. Here, we investigated whether interaction exists between 5-HT_1A receptor and genes encoding key members in brain 5-HT system. Chronic treatment with selective agonist of 5-HT_1A receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) produced considerable decrease in hypothermic response to acute administration of 8-OH-DPAT in CBA/Lac mice indicating desensitization of 5-HT_1A receptors. The decrease in 5-HT_1A gene expression as well as decrease in the expression of gene encoding key enzyme in 5-HT synthesis, tryptophan hydroxylase-2 (TPH-2) in the midbrain, and the expression of the gene encoding 5-HT_2A receptor in the frontal cortex was shown. There were no significant changes in 5-HT transporter mRNA level in the midbrain. Despite considerable decrease in the expression of the genes encoding tryptophan hydroxylase-2, 5-HT_1A and 5-HT_2A receptors, chronic 8-OH-DPAT treatment failed to produce significant changes in 5-HT_1A-linked behavior (intermale aggression, open-field behavior, light-dark box, and pinch-induced catalepsy), suggesting compensatory and adaptive effect of genes suppression. The obtained data on the effect of 8-OH-DPAT-induced desensitization of 5-HT_1A receptors on 5-HT_1A, 5-HT_2A and TPH-2 gene expression demonstrated the role of 5-HT_1A receptor as indirect regulator of gene expression. The results provide the first evidence of receptor-key genes interaction in brain 5-HT system and may have profound implications in understanding the functioning of the brain neurotransmitter systems.     

Effect of Selective Agonist of Serotonin 5-HT<Subscript>1A</Subscript> Receptors on Defensive Behavior in Mice with Different Predisposition to Catalepsy

We studied the effect of activation of serotonin 5-HT_1A receptors with selective agonist 8-OHDPAT (0.1, 0.5, and 1.0 mg/kg) on intraspecies aggression and freezing reaction (catalepsy) in male mice of catalepsy-resistant AKR/J and two catalepsy-prone strains CBA/Lac and congenic AKR.CBA-D13Mit76. The latter strain differs from AKR strain only by terminal chromosome 13 fragment transferred from CBA strain and containing a locus determining predisposition to catalepsy and a gene encoding 5-HT_1A receptor. 8-OH-DPAT in a low dose (0.1 mg/kg) affecting primarily presynaptic receptors suppressed aggressive behavior in CBA mice, but had no effect on the time of cataleptic freezing. At the same time, this dose of the drug produced no significant effect on aggression in AKR and AKR.CBA-D13Mit76 mice, but significantly attenuated freezing in AKR.CBA-D13Mit76 mice. High doses of 8-OHDPAT (0.5 and 1 mg/kg) which affected mainly postsynaptic receptors inhibited catalepsy in CBA and AKR.CBA-D13Mit76 mice and in a dose of 1 mg/kg it suppressed aggression in all tested mouse strains. We concluded that the genome of the recipient strain (AKR) modulated the involvement of 5-HT_1A receptors into the regulation of aggression and catalepsy in mice.     

Immune Responses on Activation of Pre- and Postsynaptic Serotonin 5-HT1A Receptors in Mice with Depression-Like States

The development of a depression-like state in C57BL/6 J mice is accompanied by significant reductions in immune responses. Administration of the selective agonist of 5-HT_1A receptors 8-OH-DPAT to these animals at doses affecting both presynaptic receptors (0.1 mg/kg) and postsynaptic receptors (1.0 mg/kg) did not alter the number of IgM antibody-forming cells (AFC) in the spleen at the peak of the immune response, i.e., day 4 after administration of sheep erythrocytes, in mice with depression-like behavior. At the same time, activation of presynaptic 5-HT_1A receptors in control mice (without experience of victory or defeat) induced increases in the immune response, while stimulation of postsynaptic receptors led to immunosuppression. The question of decreases in the sensitivity of pre- and postsynaptic 5-HT_1A receptors during formation of depression-like behavior and the role of the functional activity of this type of receptor in the development of the immune responses in these conditions is discussed.     

Identification of neonatal rat hippocampal radial glia cells in vitro

Activation of central 5-HT₃ receptors by the selective agonist m-CPBG (1-(3-chlorophenyl)biguanide hydrochloride, 40 nM i.c.v.) produced stronger hypothermic effect in mice than activation of 5-HT_1A receptors by their agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propilamino)tetralin) injected by the same route at an equimolar dose. The hypothermic effect of m-CPBG was realized by influence on both the heat production and the heat loss: oxygen consumption and CO₂ expiration were decreased; heat dissipation determined by the tail skin temperature was increased. The heat loss effect of 5-HT₃ receptors was significantly shorter than the decrease in metabolism indicating the prevalent role of heat production decrease in 5-HT₃ receptor-induced deep and long-lasing hypothermia. In addition, the decrease in the respiratory exchange ratio (RER) was shown suggesting that the activation of the 5-HT₃ receptors switched metabolism to prevalent use of lipids as the main energetic substrate. 5-HT_1A receptor agonist 8-OH-DPAT (40 nM i.c.v.) produced less depressing effect on general metabolism: a decrease in oxygen consumption and CO₂ excretion began later and was not so deep as after m-CPBG administration. Heat-loss effect of 5-HT_1A receptors activation was not observed. In contrast to m-CPBG effect, RER after 5-HT_1A receptors activation raised immediately after injection and then gradually decreased to the values observed in m-CPBG-treated mice. Obtained results show that activation of central 5-HT₃ receptors are more effective in hypothermia induction due to marked decrease in thermogenesis and increase in heat loss.     

Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT1A and 5-HT2A receptors functional activity and expression of key genes of the brain serotonin system

Among serotonin (5-HT) receptors, the 5-HT₃ receptor is the only ligand-gated ion-channel. Little is known about the interaction between the 5-HT₃ receptor and other 5-HT receptors and influence of 5-HT₃ chronic activation on other 5-HT receptors and the expression of key genes of 5-HT system. Chronic activation of 5-HT₃ receptor with intracerebroventricularly administrated selective agonist 1-(3-chlorophenyl)biguanide hydrochloride (m-CPBG) (14 days, 40 nmol, i.c.v.) produced significant desensitization of 5-HT₃ and 5-HT_1A receptors. The hypothermic responses produced by acute administration of selective agonist of 5-HT₃ receptor (m-CPBG, 40 nmol, i.c.v.) or selective agonist of 5-HT_1A receptor (8-hydroxy-2-(di-n-propylamino)tetralin) (8-OH-DPAT, 1 mg/kg, i.p.) was significantly lower in m-CPBG treated mice compared with the mice of control groups. Chronic m-CPBG administration failed to induce any significant change in the 5-HT_2A receptor functional activity and in the expression of the gene encoding 5-HT_2A receptor. Chronic activation of 5-HT₃ receptor produced no considerable effect on the expression on 5-HT₃, 5-HT_1A, and 5-HT transporter (5-HTT) and tryptophan hydroxylase-2 (TPH-2) genes – the key genes of brain 5-HT system, in the midbrain, frontal cortex and hippocampus. In conclusion, chronic activation of ionotropic 5-HT₃ receptor produced significant desensitization of 5-HT₃ and postsynaptic 5-HT_1A receptors but caused no considerable changes in the expression of key genes of the brain 5-HT system.     

Effects of activation and blockade of dopamine D<Subscript>2</Subscript> receptors on the immune response in mice with different types of behavior

Activation of dopamine D₂ receptors by the selective agonist quinpirole was found to lead to immunostimulation in control (no experience of confrontations) C57BL/6J mice and in mice subjected to psychoemotional tension (aggression and submission). The most marked increase in the immune response was seen on formation of the aggressive and submissive behavioral strategies. The effects of blockade of D₂ dopamine receptors by haloperidol-immunosuppression-were seen only in control and aggressive animals, but were not seen in animals with submissive behavior. The question of the significance of the initial psychoemotional state, which is linked with particular neurotransmitter patterns in the brain (levels of dopamine, serotonin, their metabolites; dopamine receptor activity in subcortical structures), for the effects of agents altering the activity of dopamine D₂ receptors on the immune response is discussed. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 5, pp. 552–559, May, 2006.     

Effects of Chronic Fluoxetine Treatment on Catalepsy and the Immune Response in Mice with a Genetic Predisposition to Freezing Reactions: The Roles of Types 1A and 2A Serotonin Receptors and the tph2 and SERT Genes

ASC (Antidepressant-Sensitive Catalepsy) mice, bred for a high predisposition to catalepsy, are characterized by depression-like behavior and decreased immune responses. Chronic administration of fluoxetine, which is a selective serotonin reuptake inhibitor antidepressant widely used in clinical practice, to mice of this strain weakened catalepsy and normalized the number of rosette-forming cells in the spleen. In mice of the parental cataleptic strain CBA/Lac, fluoxetine had no effect on the level of catalepsy or the immune response. Analysis of the effects of fluoxetine on the functional activity of 5-HT_1A and 5-HT_2A receptors, and the expression of 5-HT_1A receptor genes in the frontal cortex and midbrain and 5-HT_2A receptors in the frontal cortex, as well as the tryptophan hydroxylase-2 and the serotonin transporter genes in the midbrain showed that the antidepressant had no effect on these parameters in ASC mice, but decreased the functional activity of 5-HT_2A receptors in CBA/Lac mice. The possibility that the actions of fluoxetine on catalepsy and the immune response in mice with depression-like states are mediated via other serotoninergic mechanisms is discussed.     

5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat

The serotoninergic system and the 5-HT_1A receptors have been involved in the brain response to acute stress. The aim of our study was evaluate the role of the 5-HT_1A receptors in serotoninergic cells of rostral and caudal raphe nuclei under acute immobilization in rats. Double immunocytochemical staining of 5-hydroxy-tryptamine and c-Fos protein and stereology techniques were used to study the specific cell activation in the raphe nuclei neurons in five groups (control group, immobilization group (immobilization lasting 1 h), DPAT group (8-OH-DPAT 0.3 mg/kg, s.c.), DPAT + IMMO group (8-OH-DPAT 0.3 mg/kg, s.c., 30′ prior acute immobilization) and WAY + DPAT + IMMO group (WAY-100635 0.3 mg/kg, s.c. and 8-OH-DPAT 0.3 mg/kg, s.c., 45′ and 30′, respectively, before immobilization). Our results showed an increase in the number of c-Fos immunoreactive nuclei in serotoninergic cells in both dorsal and median raphe nuclei in the immobilized group. The 8-OH-DPAT pretreatment counteracted the excitatory effects of the acute immobilization in these brain regions. In addition, WAY-100635 administration reduced the effect of 8-OH-DPAT injection, suggesting a selective 5-HT_1A receptor role. Raphe pallidus and raphe obscurus did not show any differences among experimental groups. We suggest that somatodendritic 5-HT_1A receptors in rostral raphe nuclei may play a crucial role in both mediating the consequences of uncontrollable stress and the possible beneficial effects of treatment with 5-HT_1A receptor agonists.     

Central 5-HT3 receptor-induced hypothermia in mice: Interstrain differences and comparison with hypothermia mediated via 5-HT1A receptor

The selective agonist of serotonin 5-HT₃ receptor 1-(3-chlorophenyl)biguanide hydrochloride (m-CPBG) administered intracerebroventricularly (40, 80 or 160 nmol) produced long-lasting dose-dependent hypothermic response in AKR/2J mice. m-CPBG (160 nmol i.c.v.) induced profound hypothermia (delta t = −4 °C) that lasted up to 7 h. m-CPBG (40 nmol i.c.v.)-induced hypothermia was attenuated by 5-HT₃ receptor antagonist ondansetron pretreatment. At the same time, intraperitoneal administration of m-CPBG in a wide range of doses (0.5, 1.0, 5.0 or 10.0 mg/kg) did not affect the body temperature. These findings indicate: (1) the implication of central, rather than peripheral 5-HT₃ receptor in the thermoregulation; (2) the inability of m-CPBG to cross blood–brain barrier in mice. The comparison of brain 5-HT₃-induced hypothermic reaction in six inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J) was performed and two highly sensitive to m-CPBG strains (CBA/Lac and C57BL/6) were found. In the same six mouse strains the functional activity of 5-HT_1A receptor was studied. The comparison of hypothermic reactions produced by 5-HT_1A receptor agonist 8-OH-DPAT (1.0 mg/kg i.p.) and m-CPBG revealed significant correlation between 5-HT₃ and 5-HT_1A-induced hypothermia in five out of six investigated mouse strains. 5-HT_1A receptor antagonist p-MPPI pretreatment (1 mg/kg i.p.) diminished hypothermia produced by centrally administered m-CPBG (40 nmol i.c.v.). The data suggest the cross-talk between 5-HT_1A and 5-HT₃ receptors in the mechanism of 5-HT-related hypothermia.     

Serotonin 5-HT2 and 5-HT1A-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster

Aggressive behavior is widespread throughout the animal kingdom, and is a complex social behavior influenced by both genetics and environment. Animals typically fight over resources that include food, territory, and sexual partners. Of all the neurotransmitters, serotonin (5-HT) has been the most implicated in modulating aggressive behaviors in mammalian systems. In the fruit fly, Drosophila melanogaster, the involvement of 5-HT itself in aggressive behaviors has been recently established, however, the underlying mechanisms have largely remained elusive. Here we describe the influence of different 5-HT receptor subtypes on aggressive behaviors in Drosophila. Drosophila express homologs of three mammalian 5-HT receptors: the 5-HT_1A, 5-HT₂, and 5-HT₇ receptors. Significantly, these receptors mediate important behaviors in mammalian systems ranging from feeding, aggression, and sleep, to cognition. To examine the role of the 5-HT₂Dro receptor, we utilized the selective 5-HT₂ receptor agonist (R)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), and the 5-HT₂ receptor antagonist, ketanserin. To examine the role of 5-HT_1A-like receptors we used the 5-HT_1A receptor agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), and the 5-HT_1A receptor antagonist WAY100635. We find that activation of 5-HT₂ receptors with (R)-DOI appears to decrease overall aggression, whereas activation of 5-HT_1A-like receptors with 8-OH-DPAT increases overall aggression. Furthermore, the different 5-HT receptor circuitries appear to mediate different aspects of aggression: 5-HT₂ receptor manipulation primarily alters lunging and boxing, whereas 5-HT_1A-like receptor manipulation primarily affects wing threats and fencing. Elucidating the effects of serotonergic systems on aggression in the fly is a significant advancement not only in establishing the fly as a system to study aggression, but as a system relevant to elucidating molecular mechanisms underlying aggression in mammals, including humans.     

Chronic Actions of Thyroxine on Behavior and Serotonin Receptors in Mouse Strains with Contrasting Predispositions to Catalepsy

The studies reported here addressed the effects of chronic administration of thyroxine (2 mg/liter for 60 days) on catalepsy and the functional activity and expression of the 5-HT_1A and 5-HT_2A receptor genes in the brains of adult male mice of the cataleptic ASC strain and the catalepsy-resistant AKR strain. Thyroxine induced cataleptics in AKR mice but had anticataleptic activity in ASC animals. Chronic thyroxine administration increased the functional activity and expression of 5-HT_2A receptors in the frontal cortex in AKR mice but not in ASC mice. In ASC mice, the hormone significantly weakened the hypothermic effect of the 5-HT_1A receptor agonist 8-OH-DPAT, though it did not alter the expression of these receptors. These results suggest that 5-HT_2A receptors are involved in the cataleptogenic while 5-HT_1A receptors are involved in the anticataleptic effects of the hormone in mice.     

The Effects of Hypothyroidism on 5-HT1A and 5-HT2A Receptors and the Serotonin Transporter Protein in the Rat Brain

The effects of hypothyroidism on 5-HT_1A and 5-HT_2A receptors and the serotonin transporter protein were studied in thyroidectomized male Wistar rats in two experimental groups: 1) animals kept on an iodine-free diet (hypothyroid rats) and 2) animals kept on thyroxine (15 g/kg) for 21 days (giving normal thyroid hormone levels, euthyroid animals). Sham-operated rats served as controls. Binding of [³H]8-OH-DPAT with 5-HT_1A receptors and [³H]citalopram with the transporter protein in the hippocampus and midbrain showed no changes in hypothyroid rats as compared with controls. Conversely, there were significant decreases in [³H]ketanserin binding to 5-HT_2A receptors in the frontal cortex in hypothyroid rats as compared with controls; this decrease was reversed by thyroxine treatment. Thus, losses of cortical 5-HT_2A receptors appears to be the main consequence of hypothyroidism at the level of the serotonin system of the brain.     

Functional Characteristics of Serotonin 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>2C</Subscript> Receptors in the Brain and the Expression of the 5-HT<Subscript>2A</Subscript> and 5-HT<Subscript>2C</Subscript> Receptor Genes in Aggressive and Non-Aggressive Rats

The functional activity of serotonin 5-HT_2A and 5-HT_2C receptors and the expression of the genes encoding them were studied in Norway rats bred for 60 generations for the presence and absence of high levels of stress-evoked aggression to humans. There were no significant differences in the levels of 5-HT_2A receptor mRNA in the midbrain, frontal cortex, and hippocampus and the extents of head twitching evoked by the 5-HT_2A agonist DOI in rats with and without genetically determined high levels of aggression. Administration of the selective 5-HT_2C agonist MK-212 weakened reflex startle in response to an acoustic signal (the acoustic startle response) in non-aggressive animals but had no significant effects on the response in aggressive animals. Increases in the level of 5-HT_2C receptor mRNA were seen in the frontal cortex and hippocampus in non-aggressive rats as compared with aggressive animals. Increases in the expression of the 5-HT_2C receptor gene and the functional state of 5-HT_2C receptors were seen in the brains of non-aggressive rats, without any changes in the 5-HT_2A receptor mRNA level or receptor sensitivity; this is evidence for the involvement of 5-HT_2C receptors in the mechanisms inhibiting fear-evoked aggressive behavior.     

UHF-dielectrometry of the urine in prognosis of aggregation stability

The hypothermic effects of 5-HT_1A serotonin receptor agonist 8-OH-DPAT after intranasal, intraperitoneal, and subcutaneous administration were compared. In a dose of 1 mg/kg 8-OH-DPAT induced similar thermal reactions after administration by all three routes. In a dose of 0.5 mg/kg 8-OH-DPAT caused no appreciable changes in body temperature after intraperitoneal injection and decreased it after subcutaneous and intranasal administration. No genotypic differences in the effects of 5-HT_1A receptor agonist administered by different routes were detected in four inbred mouse strains. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 413-415, October, 2008