RESUMO
Nitric oxide (NO) release in the right medial prefrontal cortex (RmPFC) produces anxiogenesis. In the bed nucleus of the stria terminalis (BNST), a region that receives neuronal projections from the mPFC, NO provokes anxiety, an effect that is blocked by local injections of corticotrophin-releasing factor type 1 receptor (CRF1) or n-methyl-d-aspartate receptor (NMDAr) antagonist. Anxiety is also enhanced by social defeat stress, and chronic stress impairs and facilitates, respectively, PFC and BNST roles in modulating behavioral responses to aversive situations. This study investigated whether the (i) chronic social defeat stress (CSDS) increases NO signaling in the mPFC; and/or (ii) anxiogenic effects provoked by the intra-RmPFC injection of NOC-9 (an NO donor) or by CSDS are prevented by intra-BNST injections of AP-7 (0.05 nmol) or CP 376395 (3.0 nmol), respectively, NMDAr and CRF1 antagonists, in male Swiss-Webster mice exposed to the elevated plus-maze (EPM). Results showed that (a) CSDS increased anxiety (i.e., reduced open-arm exploration) and repeatedly activated nNOS-containing neurons, as measured by ΔFosB (a stable nonspecific marker of neural activity) + nNOS double-labeling, in the right (but not left) mPFC, (b) NOC-9 in the RmPFC also increased anxiety, and (c) both CSDS and NOC-9 effects were reversed by injections of AP-7 or CP 376395 into the BNST. These results suggest that NMDA and CRF1 receptors located in BNST play an important role in the modulation of anxiety provoked by NO in the RmPFC, as well as by chronic social defeat in mice.
Assuntos
Ansiedade/metabolismo , Óxido Nítrico/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Núcleos Septais/metabolismo , Derrota Social , Aminopiridinas/administração & dosagem , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Microinjeções , Óxido Nítrico/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Núcleos Septais/efeitos dos fármacos , Triazenos/administração & dosagemRESUMO
It has been suggested that the left medial prefrontal cortex (LmPFC) has an inhibitory role in controlling the right mPFC (RmPFC), thereby reducing the deleterious effects of stressors on emotional states. Here, we investigated the effects on anxiety of bilateral or unilateral injections of NOC-9 [a nitric oxide (NO) donor] and cobalt chloride (CoCl2; a synaptic inhibitor) into the mPFC of mice exposed to the elevated plus-maze (Experiments 1 and 2). The effects of restraint or social defeat on anxiety in undrugged mice were recorded at 5 min or 24 h after exposure to the stress (Experiment 3). Experiment 4 investigated the effects of LmPFC injection of CoCl2 combined with restraint or social defeat on anxiety, which was recorded 24 h later. Although intra-RmPFC NOC-9 produced anxiogenesis, its injection into the LmPFC, or bilaterally, did not change anxiety. Intra-RmPFC or -LmPFC injection of CoCl2 produced anxiolytic- and anxiogenic-like effects, respectively. Both restraint and social defeat produced anxiogenesis at 5 min, but defeated mice did not display anxiety 24 h after the stress. Although intra-LmPFC CoCl2 did not change anxiety, which was recorded 24 h later in non-stressed mice, this synaptic inhibitor produced a clear, anxiogenic-like effect in defeated (but not restrained) mice. These results suggest that (i) nitrergic activation of the RmPFC increases anxiety, which in turn is inhibited by NO production within the LmPFC; (ii) neuronal inhibition of the RmPFC or LmPFC elicits anxiolysis and anxiogenesis, respectively; and (iii) inactivation of the LmPFC results in recrudescence of anxiety induced by social defeat stress.
Assuntos
Ansiedade/metabolismo , Lateralidade Funcional/fisiologia , Óxido Nítrico/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Cobalto/administração & dosagem , Relação Dose-Resposta a Droga , Lateralidade Funcional/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Triazenos/administração & dosagemRESUMO
It has been shown that the bed nucleus of the stria terminalis (BNST) of rats contains nitrergic neurons, which are activated during animal exposure to aversive stimuli. The BNST is also populated by glutamatergic and corticotrophin releasing factor (CRFergic) neurons, which in turn are activated under stressful situations. Here we investigated the anxiogenic-like effects of intra-BNST injections of a nitric oxide (NO) donor, NOC-9 in mice. The role of CRFergic and glutamatergic systems on defensive behavior induced by NOC-9 was investigated with previous intra-BNST infusion of different doses of CP376395, a CRF type 1 receptor antagonist (CRF1), or AP-7, an NMDA (N-methyl-D-aspartate) receptor antagonist. Anxiety-like behavior was assessed immediately and 5 min after intra-BNST drug injection, exposing mice to a novel arena and to the elevated plus-maze (EPM; an anxiogenic situation). Results showed that NOC-9 provoked a short period (≈ 150 s) of freezing behavior in the novel arena and increased anxiety in the EPM. Both CP and AP-7 attenuated the anxiogenic-like effects of NOC-9 in the EPM without changing freezing behavior in the novel arena. When given alone (i.e. without prior intra-BNST injection of NOC-9), AP-7 (0.20 nmol), but not CP (0.75, 1.50, or 3.00 nmol), attenuated anxiety in mice exposed to the EPM. These results suggest that CRF1 and NMDA receptors located within the BNST differentially modulate aversive effects induced by NO production in this limbic forebrain structure.
Assuntos
Ansiedade/induzido quimicamente , Óxido Nítrico/farmacologia , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Núcleos Septais/efeitos dos fármacos , Aminopiridinas/farmacologia , Animais , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Reação de Congelamento Cataléptica/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Triazenos/farmacologiaRESUMO
The anxiogenic and antinociceptive effects produced by glutamate N-methyl-D-aspartate receptor activation within the dorsal periaqueductal gray (dPAG) matter have been related to nitric oxide (NO) production, since injection of NO synthase (NOS) inhibitors reverses these effects. dPAG corticotropin-releasing factor receptor (CRFr) activation also induces anxiety-like behavior and antinociception, which, in turn, are selectively blocked by local infusion of the CRF type 1 receptor (CRFr1) antagonist, NBI 27914 [5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6-trichlorophenyl)aminopyridine]. Here, we determined whether i) the blockade of the dPAG by CRFr1 attenuates the anxiogenic/antinociceptive effects induced by local infusion of the NO donor, NOC-9 [6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine], and ii) the anxiogenic/antinociceptive effects induced by intra-dPAG CRF are prevented by local infusion of Nω-propyl-L-arginine (NPLA), a neuronal NOS inhibitor, in mice. Male Swiss mice (12 weeks old, 25-35 g, N = 8-14/group) were stereotaxically implanted with a 7-mm cannula aimed at the dPAG. Intra-dPAG NOC-9 (75 nmol) produced defensive-like behavior (jumping and running) and antinociception (assessed by the formalin test). Both effects were reversed by prior local infusion of NBI 27914 (2 nmol). Conversely, intra-dPAG NPLA (0.4 nmol) did not modify the anxiogenic/antinociceptive effects of CRF (150 pmol). These results suggest that CRFr1 plays an important role in the defensive behavior and antinociception produced by NO within the dPAG. In contrast, the anxiogenic and antinociceptive effects produced by intra-dPAG CRF are not related to NO synthesis in this limbic midbrain structure.
Assuntos
Animais , Masculino , Camundongos , Comportamento Animal/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Triazenos/farmacologia , Óxido Nítrico Sintase/farmacologia , Óxido Nítrico/farmacologia , Substância Cinzenta Periaquedutal/fisiologia , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/fisiologiaRESUMO
The anxiogenic and antinociceptive effects produced by glutamate N-methyl-D-aspartate receptor activation within the dorsal periaqueductal gray (dPAG) matter have been related to nitric oxide (NO) production, since injection of NO synthase (NOS) inhibitors reverses these effects. dPAG corticotropin-releasing factor receptor (CRFr) activation also induces anxiety-like behavior and antinociception, which, in turn, are selectively blocked by local infusion of the CRF type 1 receptor (CRFr1) antagonist, NBI 27914 [5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6-trichlorophenyl)aminopyridine]. Here, we determined whether i) the blockade of the dPAG by CRFr1 attenuates the anxiogenic/antinociceptive effects induced by local infusion of the NO donor, NOC-9 [6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine], and ii) the anxiogenic/antinociceptive effects induced by intra-dPAG CRF are prevented by local infusion of N(ω)-propyl-L-arginine (NPLA), a neuronal NOS inhibitor, in mice. Male Swiss mice (12 weeks old, 25-35 g, N = 8-14/group) were stereotaxically implanted with a 7-mm cannula aimed at the dPAG. Intra-dPAG NOC-9 (75 nmol) produced defensive-like behavior (jumping and running) and antinociception (assessed by the formalin test). Both effects were reversed by prior local infusion of NBI 27914 (2 nmol). Conversely, intra-dPAG NPLA (0.4 nmol) did not modify the anxiogenic/antinociceptive effects of CRF (150 pmol). These results suggest that CRFr1 plays an important role in the defensive behavior and antinociception produced by NO within the dPAG. In contrast, the anxiogenic and antinociceptive effects produced by intra-dPAG CRF are not related to NO synthesis in this limbic midbrain structure.
Assuntos
Comportamento Animal/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Triazenos/farmacologia , Animais , Masculino , Camundongos , Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/farmacologia , Substância Cinzenta Periaquedutal/fisiologia , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/fisiologiaRESUMO
A single exposure to the elevated plus-maze test (EPM) increases open arms avoidance and reduces or abolishes the anxiolytic-like effect of benzodiazepines assessed during a second trial, a phenomenon defined as "one-trial tolerance" (OTT). It has been emphasized that the dorsal portion of the midbrain periaqueductal gray (dPAG) plays a role on this enhanced aversion phenomenon in maze-experienced rodents. Given that intra-dPAG injections of a wide range of serotonergic 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptor agonists produce anxiolytic-like effects in maze-naïve rodents, the present study examined the effects of the 5-HT(1A) receptor agonist 8-OH-DPAT (5.6 and 10.0nmol in 0.15microl) the preferential 5-HT(2A) receptor agonist DOI (2.0 and 8.0nmol in 0.1microl) and the preferential 5-HT(2C) receptor agonist MK-212 (21.2 and 63.6nmol in 0.1microl) microinjected into the dPAG prior to Trial 1 and Trial 2 on the behaviour of mice in the EPM. Test sessions were recorded and subsequently scored for anxiety-like behaviour (percentage of open arms entries and time) as well as general locomotor activity (closed arm entries). The results showed a lack of 8-OH-DPAT (5.6 and 10.0nmol) effect on the behaviour of maze-naïve and maze-experienced mice, while intra-dPAG microinfusions of DOI (8nmol) reduced anxiety-like behaviour only in maze-experienced mice that had received a similar treatment prior to Trial 1. Furthermore, intra-dPAG MK-212 (63.6nmol) showed an anxiolytic-like effect on both Trial 1 and Trial 2. Importantly, these effects were observed in the absence of any significant change in closed arm entries, the parameter considered to be a valid index of locomotor activity in the plus-maze. These results support the dPAG as a crucial structure involved in the neurobiology of the OTT phenomenon as well as accounting the role of the 5-HT(2A) and 5-HT(2C) receptors located within this midbrain structure on the emotional state induced by EPM test and retest paradigm mice.
Assuntos
Ansiedade/patologia , Aprendizagem em Labirinto/fisiologia , Substância Cinzenta Periaquedutal/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Anfetaminas/farmacologia , Análise de Variância , Animais , Ansiedade/fisiopatologia , Comportamento Animal , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Microinjeções/métodos , Atividade Motora/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Pirazinas/farmacologia , Reprodutibilidade dos Testes , Agonistas do Receptor 5-HT1 de Serotonina , Agonistas do Receptor 5-HT2 de Serotonina , Serotoninérgicos/farmacologiaRESUMO
In order to investigate the relationship between behaviors elicited by chemical stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid (5 nmol in 0.1 micro l), was infused into the dorsal PAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period following drug infusion, more jumps were made in the chamber than in the MDTB runway but running time and distance traveled were significantly higher in the runway. Animals were subsequently tested using the standard MDTB procedure (anti-predator avoidance, chase and defensive threat/attack). No drug effects on these measures were significant. In a further test in the MDTB apparatus, the pathway of the mouse during peak locomotion response was blocked 3 times by the predator stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety percent of D,L-homocysteic treated animals made direct contact with the stimulus (rat), indicating that D,L-homocysteic-induced running is not guided by relevant (here, threat) stimuli. These results indicate that running as opposed to jumping is the primary response in mice injected with D,L-homocysteic into the dorsal PAG when the environment enables flight. However, the lack of responsivity to the predator during peak locomotion suggests that D,L-homocysteic-stimulation into the dorsal PAG does not induce normal antipredator flight.
Assuntos
Comportamento Animal , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Medo , Homocisteína/administração & dosagem , Camundongos , Substância Cinzenta Periaquedutal/fisiologiaRESUMO
We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT(2B/2C) receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT(2B/2C) receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species.
Assuntos
Ansiedade/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Reação de Fuga/fisiologia , Aprendizagem em Labirinto/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Análise de Variância , Animais , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Depressores do Apetite/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Cafeína/farmacologia , Carbolinas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Relação Dose-Resposta a Droga , Reação de Fuga/efeitos dos fármacos , Imipramina/farmacologia , Inibição Psicológica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Distribuição Aleatória , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Serotoninérgicos/farmacologia , Ioimbina/farmacologiaRESUMO
RATIONALE: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. OBJECTIVE: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. METHODS: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT, NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. RESULTS: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 microl) or NAN-190 (5.6 nmol and 10 nmol/0.4 microl) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 microl) blocked both OAIA and anxiety. CONCLUSIONS: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are "recruited" during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.
Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Tonsila do Cerebelo/fisiologia , Analgesia/psicologia , Ansiolíticos/farmacologia , Ansiedade/psicologia , Midazolam/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , Animais , Ansiolíticos/administração & dosagem , Masculino , Camundongos , Microinjeções , Midazolam/administração & dosagem , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/efeitos dos fármacos , Piperazinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT1 de Serotonina , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/administração & dosagemRESUMO
The elevated T-maze has been developed as an animal model of anxiety to generate both conditioned and unconditioned fears in the same rat. This study explores a version of the elevated T-maze fit for mice. Inhibitory (passive) avoidance- conditioned fear-is measured by recording the latency to leave the enclosed arm during three consecutive trials. One-way escape- unconditioned fear-is measured by recording the time to withdraw from open arms. The results showed that mice do not appear to acquire inhibitory avoidance in the standard T-maze, since their latencies to leave enclosed arm did not increase along trials. Nevertheless, the open arms seemed to be aversive for mice, because the latency to leave the enclosed arm after the first trial was lower in a T-maze with the three enclosed arms than in the standard elevated T-maze. In agreement, the exposure of mice to an elevated T-maze without shield, that reduces the perception of openness, increased significantly the latencies to leave the enclosed arm. However, the absence of the shield also increased the time taken to leave the open arms when compared to that recorded in standard T-maze. Systematic observation of behavioral items in the enclosed arm has shown that risk assessment behavior decreases along trials while freezing increases. In the open arms, freezing did not appear to influence the high latency to leave this compartment, since mice spend only about 8% of their time exhibiting this behavior. These results suggest that mice acquire inhibitory avoidance of the open arms by decreasing and increasing time in risk assessment and freezing, respectively, along three consecutive trials. However, one-way escape could not be characterized. Therefore, there are important differences between mice (present results) and rats (previously reported results) in the performance of behavioral tasks in the elevated T-maze.