A comparison of morphine-induced locomotor activity and mesolimbic dopamine release in C57BL6, 129Sv and DBA2 mice

Inbred mouse strains show marked variations in morphine-induced locomotion and reward behaviors. As increases in mesolimbic dopamine release and locomotion have been implicated as being critical aspects of drug-seeking and reward-related behaviors, the present study sought to determine the relationship between morphine-induced changes in locomotion and mesolimbic dopamine release. Freely moving microdialysis of the ventral striatum was performed in mouse strains chosen on the basis of their documented differences in locomotor and reward response to morphine (C57BL6 and DBA2) and use in the production of genetically modified mice (129Sv). Both C57BL6 and 129Sv mice showed significant increases in locomotion and ventral striatal extracellular dopamine levels following subcutaneous morphine administration (3 mg/kg), with the former strain showing the largest increase in both parameters. Ventral striatal extracellular DA levels increased in DBA2 mice to a similar extent as 129Sv mice following morphine administration, despite this strain showing no locomotor response. Intra-strain analysis found no correlation between morphine-induced locomotion and mesolimbic dopamine release in any of the strains studied. Thus, no universal relationship between morphine-induced mesolimbic dopamine release and locomotion exists between, and particularly within, inbred mouse strains. Furthermore, morphine-induced increases in mesolimbic activity correlate negatively with the rewarding potential of morphine described in previously reported conditioned place preference studies.     

Potentiation by caffeine of the frequencies of micronuclei induced by mitomycin C and cyclophosphamide in young mice

Employing the micronucleus test in mouse bone marrow and in fetal mouse liver, the possible clastogenicity of caffeine as well as its influence on MMC- and CP-induced micronucleus levels were studied. The treatment of male and female C57Bl or BDF1 (C57Bl x DBA2) mice with caffeine (1 or 3 x 50 mg/kg and 100 mg/kg, s.c.) had no clastogenic effect in mouse bone marrow or in the fetal livers and maternal bone marrow when pregnant mice were injected with caffeine on day 16-17 of gestation. MMC (2.0 mg/kg, i.p.) increased up to 10-30-fold the number of MNPCEs in bone marrow compared to a 3-7 fold elevation of MNPCEs in fetal liver. A similar effect was also established in pregnant mice treated with CP (30 mg/kg, i.p.). No significant sex differences in spontaneous and MMC- or CP-induced MNPCEs levels were established in C57Bl and BDF1 mice. However, a significantly higher spontaneous rate of MNPCEs as well as a better-expressed responsiveness to the clastogenic activity of MMC and CP were established in C57Bl compared to BDF1 mice. The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57Bl mice compared to virgin female animals. The combined treatment of mice with caffeine (3 x 100 mg/kg) and MMC or CP caused an up to 45-49% potentiation of clastogenesis in the bone marrow of male, female and pregnant female C57Bl and BDF1 mice but not in fetal mouse livers.     

Effects of caffeine on social behavior, exploration and locomotor activity: interactions with ethanol

The effects of caffeine and its interaction with ethanol were examined in a test of social behavior and a holeboard test of exploration and locomotion. Male mice were injected i.p. with 15, 30 or 60 mg/kg caffeine alone or in combination with 2 g/kg ethanol. The animals were then put in pairs into a familiar arena, or examined individually in the holeboard. Only the highest dose of caffeine (60 mg/kg) had a significant effect on the time spent in social interaction and motor activity in the social behavior test: both measures were reduced. The duration and frequency of avoidance-irritability behavior was dose-dependently increased by caffeine. In the holeboard, caffeine caused a dose-dependent increase in locomotor activity. 30 mg/kg caffeine reversed the ethanol-induced reduction of time spent in social interaction, and 60 mg/kg caffeine antagonized the ethanol-induced increase in locomotor activity in both the social behavior and holeboard tests. Caffeine's effects on ethanol-induced behavioral changes are compared with those of other drugs.     

Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice

Colorectal distension (CRD) is a well-characterized model of visceral nociception, which we adapted to the mouse. CRD reproducibly evoked contractions of the abdominal musculature [visceromotor response (VMR)], which was graded to stimulus intensity. The magnitude of VMR was greater in male C57BL6 and female 129S6 mice than in male 129S6 and B6.129 mice. In 129S6, C57BL6, and B6.129 mice strains, VMR was reduced dose dependently by morphine (1-10 mg/kg) and by the kappa-opioid agonist U-69593 (0.2-2 mg/kg), although U-69593 was significantly less potent in C57BL6 mice. In additional experiments, the VMR was recorded from adult male 129S6 mice before and after intracolonic administration of various irritants. Only 30% ethanol significantly enhanced responses to CRD. The colon hyperalgesia persisted for 14 days and was associated with a significant shift of the morphine dose-response function to the left. We believe this will be a useful model for study of visceral nociception and hyperalgesia, including studies of transgenic mice with mutations relevant to pain.     

Acute locomotor responses to cocaine in adolescents vs. adults from four divergent inbred mouse strains

Growing evidence suggests that adolescent mice display differential sensitivity to the acute locomotor activating effects of cocaine as compared to adults, but the direction of the difference varies across studies and the reasons are not clear. Few studies have directly examined genetic contributions to age differences in locomotor stimulation from cocaine. The goal of this study was to determine the extent to which reduced stimulation in C57BL/6J adolescents as compared to adults generalizes to other strains. Therefore, we examined male and female mice from four genetically divergent inbred stains (BALB/cByJ, C57BL/6J, DBA/2J and FVB/NJ) at two ages, postnatal day 30 and postnatal day 65. Mice received either saline or cocaine (15 or 30 mg/kg), and then immediately were placed back into their home cages. Locomotor activity was recorded continuously in the home cage by video tracking. Adolescents displayed reduced stimulation as compared to adults for C57BL/6J, BALB/cByJ and female FVB/NJ mice. No age differences were observed for DBA/2J or male FVB/NJ. No main effects of sex were observed. Strain differences in pharmacokinetics, neural development or physiology could contribute to the observed differences between ages across strains. Future comparative studies could discover biological differences between strains that explain age differences in cocaine sensitivity.     

Absence of anxiolytic response to chlordiazepoxide in two common background strains exposed to the elevated plus-maze: importance and implications of behavioural baseline

Although genetic background is acknowledged as a potentially important determinant of mutant phenotypes, publications on genetically modified mice far outnumber those on progenitor strains. We have recently reported major differences in basal anxiety levels (elevated plus-maze & light/dark exploration) among three strains (C57BL/6JOlaHsd, 129/SvEv and 129S2/SvHsd) employed as progenitor stock in European laboratories (Rodgers et al. in press). Furthermore, the phenotypes of these inbred strains differed significantly from that of an outbred strain (Swiss-Webster) commonly used in behavioural pharmacology. In view of these findings, the present study assessed possible differences in the anxiolytic efficacy of chlordiazepoxide (0, 7.5 & 15.0 mg/kg, IP) in three of these strains (Swiss-Webster (SW), C57BL/6JOIaHsd (C57) & 129S2/SvHsd (129)). Experimentally naive mice were exposed to the elevated plus-maze, sessions were videotaped and behaviour analysed using ethological software. The performance of control subjects confirmed significant strain differences in basal levels of activity (SW > C57 > 129) and anxiety-related behaviours (129 = SW > C57), with hypolocomotion dominating the 129 profile. SW mice displayed an anxioselective response to both doses of chlordiazepoxide (CDP), with significant reductions in open arm avoidance and risk assessment observed in the absence of any change in general activity. In direct contrast, the lower dose of CDP (7.5 mg/kg) was without effect in either inbred strain, whereas treatment with 15.0 mg/kg induced a profile indicative of muscle relaxation/mild sedation in C57 mice and virtually abolished all behavioural activity in 129 mice. Although the absence of an anxiolytic response to CDP in C57 mice may be attributed to their low basal anxiety levels, the profile of 129 mice strongly suggests an abnormality in benzodiazepine/GABAA receptor function. The implications of these findings for research on mutant mice are discussed.     

Cocaine produces conditioned place aversion in mice with a cocaine‐insensitive dopamine transporter

Cocaine is an inhibitor of the dopamine, norepinephrine and serotonin reuptake transporters. Because its administration would elevate signaling of all these three neurotransmitters, many studies have been aimed at attributing individual effects of cocaine to specific transmitter systems. Using mice with a cocaine‐insensitive dopamine transporter (DAT‐CI mice), we previously showed that cocaine‐induced dopamine elevations were necessary for its rewarding and stimulating effects. In this study, we observe that DAT‐CI mice exhibit cocaine‐conditioned place aversion (CPA), and that its expression depends on their genetic background. Specifically, DAT‐CI mice backcrossed to the C57Bl/6J strain background did not display a preference or an aversion to cocaine, whereas DAT‐CI mice that were on a mixed 129S1/SvImJ × C57Bl/6J (129B6) background had a robust CPA to cocaine. These results indicate that while inhibition of the DAT is necessary for cocaine reward, other cocaine targets and neurotransmitter systems may mediate the aversive properties of cocaine. Furthermore, the aversive effect of cocaine can be observed in the absence of a DAT‐mediated rewarding effect, and it is affected by genomic differences between these two mouse strains.     

Reduction of caffeine teratogenicity in mice by inducing maternal drug metabolism with beta-naphthoflavone

The effect of stimulating maternal drug metabolism on caffeine teratogenicity was investigated in C57BL/6J (cytochrome P1-450 inducible) and AKR/J (cytochrome P1-450 noninducible) mice. The inducing agent, beta-naphthoflavone (beta-NF) in corn oil, was administered intraperitoneally (IP) to dams at 20 or 80 mg/kg/d on days 9 and 10 of gestation. Teratogenic injections of 175 mg/kg/d caffeine in deionized water were administered IP on days 11 and 12 of gestation. All dams were sacrificed on day 18 of gestation, and fetuses were fixed for razor blade sectioning and skeletal examination. Caffeine, without maternal metabolism stimulation, caused similar types and rates of malformations in both strains of mice. Inducing drug metabolism during pregnancy with beta-NF protected the embryos from the congenital toxicities of large injections of caffeine. Reductions in embryolethality, limb malformations, and hematoma formation were evident in the inducible strain but not in the strain incapable of being induced. A dosage of eighty mg/kg/d was more effective than 20 mg/kg/d beta-NF in decreasing malformations, suggesting that stimulation of metabolism and caffeine-induced teratogenicity are inversely related. Rapid elimination of caffeine resulting from increasing drug metabolism with the concomitant decrease in toxicity would indicate that caffeine, and not a metabolite, is the toxicant.     

Sex and strain differences in the hepatotoxic response to acute cocaine administration in the mouse

Cocaine-induced hepatotoxicity was examined in vivo in a dose-responsive manner in C57BL/6Ibg, DBA/2Ibg, C3H/2Ibg, and Balb/cJ mice. Serum glutamic-pyruvic transaminase (SGPT) activities were determined 24 hours after intraperitoneal (IP) administration of cocaine (20 to 100 mg/kg). Significant elevations (100- to 150-fold) in SGPT were observed in male mice receiving cocaine. Significant differences in sensitivity to cocaine-induced hepatotoxicity were found among males of the inbred strains, with Balb being most sensitive and C57BL being least sensitive and C3H and DBA strains exhibiting intermediate sensitivity. Female mice of the four inbred strains were more resistant than males to cocainemediated hepatotoxicity, as indicated by only twofold to tenfold elevations in SGPT values. Among the females, sensitivity of the four inbred strains—as indicated by dose response curves—fell into two categories: the sensitive strains (C3H and C57BL) and the resistant strains (Balb and DBA). Pretreatment of males of the four inbred strains with the P-450 inducer phenobarbital resulted in enhancement of cocaine-mediated hepatotoxicity in the C57BL and Balb but not the C3H and DBA mice. Phenobarbital pretreatment of females of the four inbred strains resulted in enhancement of the hepatotoxic response to cocaine in the C3H, DBA, and Balb mice. Phenobarbital-pretreated C57BL females exhibited a 100% mortality rate after the acute cocaine dose, and thus no determination of hepatotoxicity could be established for them. These data demonstrate sex and strain differences in cocaine-induced hepatotoxicity and suggest that phenobarbital pretreatment does not uniformly enhance the hepatotoxicity of cocaine.     

Behavioral differences among fourteen inbred mouse strains commonly used as disease models

We compared the behavior of 14 inbred mouse strains and an F1 hybrid commonly used in transgenic and knockout production. These strains were 129P3/J, 129S1/SvImJ, 129S6/SvEvTac, 129T2/SvEmsJ, 129X1/SvJ (formerly 129/J, 129/Sv-p+Tyr+Kitl+/J, 129/SvEvTac, 129SvEmsJ, and 129/SvJ, respectively), A/JCrTac, BALB/cAnNTac, C3H/HeNTac, C57BL/6J, C57BL/6NTac, DBA/2NTac, FVB/NTac, NOD/MrkTac, SJL/JCrNTac, and the hybrid B6129S6F1Tac. Performance in three behavioral tests (rotorod, open-field activity-habituation, and contextual and cued fear conditioning) was determined. On the rotorod assay, SJL/JCrNTac mice had the shortest latencies to fall on the first day of testing, and DBA/2NTac mice showed impaired motor learning. Open-field behavior was analyzed using the parameters total distance, center distance, velocity, and vertical activity. 129T2/EvEmsJ and A/JCrTac were least active in the open field, whereas NOD/MrkTac mice were most active. Contrary to earlier studies, we found that all strains habituated to the open field in at least one of these parameters. In contextual and cued fear conditioning, all strains displayed activity suppression. However, FVB/NTac mice reacted less strongly to both context and cue than did most of the other strains. There were no significant behavioral differences between C57BL/6J and C57BL/6NTac, except for higher open-field activity in C57BL/6J female mice. These findings illustrate the importance of the appropriate selection of background strain for transgenic, gene targeting, or drug research.     

Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity. Furthermore, the genetic background markedly influences the autoimmune phenotype of SLE in gene-targeted mice. This suggests an important role in the expression of autoimmunity of as-yet-uncharacterised background genes originating from these parental mouse strains. Using genome-wide linkage analysis, we identified several susceptibility loci, derived from 129 and C57BL/6 mice, mapped in the lupus-prone hybrid (129 × C57BL/6) model. By creating a C57BL/6 congenic strain carrying a 129-derived Chromosome 1 segment, we found that this 129 interval was sufficient to mediate the loss of tolerance to nuclear antigens, which had previously been attributed to a disrupted gene. These results demonstrate important epistatic modifiers of autoimmunity in 129 and C57BL/6 mouse strains, widely used in gene targeting. These background gene influences may account for some, or even all, of the autoimmune traits described in some gene-targeted models of SLE.     

Differential effects of pentobarbital and ethanol in mice

The duration of the loss of righting reflex (RR) after ethanol, 4 g/kg, intraperitoneally (i.p.), was significantly longer in “long-sleep” (LS) than in “short-sleep” (SS) mice. This effect was shown to be correlated with differences in brain sensitivities to ethanol. In contrast, pentobarbital sodium (PB), 50 mg/kg, i.p., produced a significantly longer loss of RR in SS than in LS mice. The PB concentrations in the brain were the same in both mouse strains at the time of RR recovery suggesting equal sensitivities of the central nervous systems to PB. The rates of disappearance of PB from the blood were the same in both strains, but the apparent volume of distribution of PB in the LS strain was greater than in SS mice.In addition, C57BL/6J mice were found to be more sensitive than DBA/2J mice to PB, 50 mg/kg. In contrast, C57BL mice are known to be less sensitive than the DBA strain to ethanol. The PB concentration in the brain of DBA mice at the recovery of the RR was significantly greater than in C57BL mice. The apparent volumes of distribution of PB were not different in the two strains, but the rate of disappearance of PB from the blood of C57BL mice was significantly greater than for the DBA strain. In conclusion, factors which govern the brain sensitivities of selected mouse strains to ethanol and pentobarbital may not be equivalent.     

The effect of dopamine receptor stimulation on the motor and stereotypic activities of mice with different genotypes]

On mice of 8 highly inbred strains--BALB/c, DBA/2, C57B1/6, CBA, DD, CC57Br, C3H/He, A/He--the role was studied of dopamine receptors of the first and second types (D1 and D2) in the regulation of the general motor activity and stereotypic climbing. Significant dependence was shown of these types of dopamine-dependent behaviour on the genotype. Agonist of D1/D2 receptors, apomorphine decreased the motor activity of animals of the all studied strains, and this effect significantly depended on the genotype. The inhibition of locomotion after selective stimulation of D2 receptors (by LY 171555) was significant. Distribution of mouse strains according to expressiveness of climbing after administration of apomorphine differed from their distribution by the level of motor activity. Selective stimulation of D1 receptors, on the whole, elicited climbing of lesser intensity than D1/D2 activation (excluding CBA strain), and administration of D2 agonist did not induce it at all. Probably, for full expression of behavioural reactions the interaction between D1 and D2 receptors is required.     

Mouse strain differences in autonomic responses to stress

In humans, anxiety disorders are often accompanied by an overactive autonomic nervous system, reflected in increased body temperature (BT) and heart rate (HR). In rodents, comparable effects are found after exposure to stress. These autonomic parameters can give important information on stress and anxiety responses in mice. In the present experiments, stress reactivity of three frequently used mouse strains [129 Sv/Ev, Swiss Webster (SW) and C57 BL/6] was assessed using their autonomic stress responses. BT, HR and activity were telemetrically measured. Undisturbed circadian rhythms already showed clear differences between the mouse strains. Hereafter, autonomic responses to stressors with increasing intensity were measured. Strain differences were found in magnitude and duration of the stress responses, especially after high-intensity stressors. Generally, C57BL/6 mice showed the largest autonomic response, SW the lowest and the 129Sv/Ev the intermediate response. Interestingly, the observed ranking in autonomic stress response does not match the behavioral stress responsivity of these strains. Finally, sensitivity to the anxiolytic diazepam (0, 1, 2, 4 and 8 mg/kg) was tested using the stress-induced hyperthermia paradigm. Pharmacological sensitivity to diazepam differed between the strains with the 129Sv/Ev being most sensitive. These studies show that simultaneous measurement of behavioral and autonomic parameters under stressful conditions contributes considerably to a better interpretation of anxiety and stress levels in mice.     

品系对小鼠胚胎干细胞分离效率的影响

为了充分利用小鼠胚胎干(ES)细胞,就必须从众多小鼠品系中分离ES细胞系。本研究通过传统的成纤维细胞饲养层法,从CD-1、129/Sv、C57BL/6J和129/Sv×C57BL/6J四种不同遗传背景的小鼠中分离得到12个ES细胞系,而从KM小鼠没有得到ES细胞系。所有的ES细胞系都具有典型的ES细胞特征,AKP染色呈阳性。从四种不同遗传背景的ES细胞系得到了包含多种组织的畸胎瘤;与桑椹胚聚合后,都得到了生殖系嵌合体。结果表明:品系对小鼠ES细胞的分离有显著影响,利用129小鼠以及包含129小鼠遗传背景的杂交小鼠都较容易分离ES细胞,由ES细胞得到生殖系嵌合体的效率在不同品系间有显著差异,从杂交ES细胞比近交ES细胞中更容易得到生殖系嵌合体。     

Spontaneous Autoimmunity in 129 and C57BL/6 Mice—Implications for Autoimmunity Described in Gene-Targeted Mice

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity. Furthermore, the genetic background markedly influences the autoimmune phenotype of SLE in gene-targeted mice. This suggests an important role in the expression of autoimmunity of as-yet-uncharacterised background genes originating from these parental mouse strains. Using genome-wide linkage analysis, we identified several susceptibility loci, derived from 129 and C57BL/6 mice, mapped in the lupus-prone hybrid (129 × C57BL/6) model. By creating a C57BL/6 congenic strain carrying a 129-derived Chromosome 1 segment, we found that this 129 interval was sufficient to mediate the loss of tolerance to nuclear antigens, which had previously been attributed to a disrupted gene. These results demonstrate important epistatic modifiers of autoimmunity in 129 and C57BL/6 mouse strains, widely used in gene targeting. These background gene influences may account for some, or even all, of the autoimmune traits described in some gene-targeted models of SLE.     

Optimal N-ethyl-N-nitrosourea (ENU) doses for inbred mouse strains

ENU is a powerful germline mutagen in the mouse, providing the opportunity to analyze the functions of large numbers of genes in the mammalian genome. In many mutagenesis experiments, it would be beneficial to exploit the advantages of inbred mouse strains. To perform an effective ENU mutagenesis screen using inbred mice, a dosage regimen is required to determine the optimal dose of ENU for that inbred strain, a time-consuming preliminary process. We have carried out dosage regimens for mutagenizing doses of ENU in ten inbred strains of mouse: 129X1/SvJ, 129S6/SvEv, A/J, BALB/cJ, BTBR/N, C3He/J, C3HeB/FeJ, C57BL/6J, C57BR/cdJ, and CBA/CaJ, and determined an optimal dose for each strain, defined by length of sterile period and number of males to survive treatment. Three strains: A/J, BALB/cJ and C57BL/6J, are able to tolerate high doses, up to 300 mg/kg body weight, and are highly recommended for mutagenesis studies.     

Effect of chronically administered methylxanthines on ethanol-induced motor incoordination in mice

The effect of chronic (10 days) administration of methylxanthines, caffeine, IBMX and theophylline on acute ethanol-induced motor incoordination has been investigated in the mice. In animals that received caffeine, 45 and 90 mg/kg/24 h, ethanol, 1.5 g/kg, produced motor incoordination significantly greater compared to that in the control groups. Significantly greater ethanol-induced motor incoordination was seen in animals fed IBMX, 30 and 60 mg/kg/24 h, compared to controls. Ethanol-induced increased motor incoordination in caffeine and IBMX-fed animals was also associated with significantly greater 3H-R-PIA binding in whole brains compared to tap water controls indicating an increase in brain adenosine binding sites. However neither motor incoordination nor 3H-R-PIA binding was altered in theophylline 75 and 150 mg/kg/24 h, fed animals. The increased motor incoordination associated with increased adenosine binding sites in the brains of caffeine and IBMX-fed animals suggests an involvement of central adenosine mechanisms in the motor incoordinating effect of ethanol and further supports our earlier suggestion for the role of adenosine in some of the central effects of ethanol.     

用适应性实验对ICR、BALB/c和C57BL/6小鼠探索行为及记忆能力的评价

用洞板仪和旷场行为红外线检测系统对远交群ICR小鼠、近交系BALB/c小鼠和近交系C57BL/6小鼠的探洞、直立和跨格行为进行了测试,并通过适应性实验比较了它们的探索行为和记忆能力。研究发现:在各项试验中,ICR小鼠表现出最强的探索能力,而C57BL/6小鼠的探索能力最差;ICR小鼠还表现出比另外两个品系小鼠更强的对新环境的适应性,其记忆也明显优于C57BL/6小鼠。实验结果提示:小鼠探洞行为的适应性实验可以用来测试小鼠的记忆能力,而小鼠的直立行为在一定程度上也反映了其对周围环境、事物的探索和认知。这些结果为今后在研究小鼠神经生物学时的行为学指标选择问题提供了参考依据,同时也提示了在进行小鼠行为学实验时,根据不同研究目的选择不同品系的重要性。     

Locomotion induced by non-contingent intracranial stimulation: comparison to psychomotor stimulant

Non-contingent experimenter-applied stimulation (nEAS) to the ventral mesencephalon, unlike contingent intracranial self-stimulation (ICSS), elicits high rates of general locomotion. This locomotion may be due to the nature of the presentation of stimulation, in that nEAS is non-contingent, while ICSS depends on a specific and focused response (e.g., bar pressing). Psychomotor stimulants also elicit high amounts of general locomotion, with the locomotion attributed to increased dopamine release. Interestingly, dopamine release decreases or is absent with repeated ICSS, but not nEAS. This suggests that the locomotion elicited by nEAS may be the result of DA release similar to that observed with psychomotor stimulants. To determine the relationship between locomotion induced by nEAS and psychomotor stimulants, locomotion elicited by nEAS was directly compared to that produced by cocaine, a psychomotor stimulant and indirect DA agonist. Six groups of rats were examined: (1) DA+ group: rats were implanted with a stimulating electrode in the ventral mesencephalon and activation of DA neurons was verified during surgery by monitoring DA release in the striatum; (2) DA- group: rats were also implanted with stimulating electrodes, but the location in the ventral mesencephalon did not elicit DA release; (3) 10-mg/kg cocaine group: rats were exposed to a low dose (10 mg/kg) of cocaine; (4) 40-mg/kg cocaine group: rats were exposed to a high dose (40 mg/kg) of cocaine; (5) saline group: rats were injected with saline; and (6) naive group: rats received no treatment. The topography of behavior was assessed in all rats during four periods: a pre-treatment baseline, treatment, early post-treatment, and a late post-treatment end point. The results suggest that locomotion elicited by nEAS was stereotypic, dependent upon DA release and similar, but not identical, to psychomotor stimulant-induced locomotion.