Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism

Parkinson’s disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals. At the same time, Selank decreased level of anxiety of rats with toxic damage of DA neurons in elevated cross shaped maze. Previously such effects of Selank were revealed in healthy rodents (rats and mice) with different models of psycho-emotional stress. Therefore, toxic damage of substantia nigra does not affect the response of the rat organism on this peptide.     

Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala

Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.     

The effects of pergolide on memory and oxidative stress in a rat model of Parkinson’s disease

One of the most widely used animal models of Parkinson’s disease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopaminergic drugs may exert brain antioxidant activity, which could explain some of their protective actions. In this way, the aim of the present study was to examine the effects of low-dose pergolide on memory deficits and brain oxidative stress in a 6-OHDA-induced rat model of PD. Right-unilateral lesions of the SN were produced with 6-OHDA. Two weeks after neurosurgery, pergolide (0.3 mg/kg/day) was injected intraperitoneally in the 6-OHDA + pergolide and sham-operated + pergolide groups, while sham-operated and 6-OHDA alone groups received saline. Radial-8-arm maze and Y-maze were used for memory assessment. We also determined some enzymatic antioxidant defenses like superoxide dismutase or glutathione peroxidase and a lipid peroxidation marker [malondialdehyde (MDA)], from the temporal lobe. A reduced number of working/reference memory errors was observed in 6-OHDA + pergolide group, compared to sham-operated rats. Additionally, post hoc analysis showed significant differences between 6-OHDA and 6-OHDA + pergolide groups in both Y-maze and radial-arm-maze tasks. We also noted a significant decrease of MDA level in the 6-OHDA + pergolide group, compared to sham-operated rats. Significant correlations were also found between behavioral parameters and MDA levels. Our data suggest that pergolide facilitates spatial memory and improves brain oxidative balance, after a 6-OHDA-induced model of PD. This could be useful for further investigations and clinical applications of pergolide.     

Effects of short- and long-acting dopamine agonists on sensitized dopaminergic neurotransmission in rats with unilateral 6-OHDA lesions

The effects of short and long-acting dopamine agonists on sensitized dopaminergic transmission in an animal model of Parkinson's disease were investigated. Rats with 6-hydroxydopamine (6-OHDA) lesions of the left nigrostriatal dopaminergic pathway were pre-exposed i.p. to 50 mg/kg methyl levodopa for 10 days. After a 7-day withdrawal period, these animals were treated with saline i.p., 0.05 mg/kg apomorphine s.c., or 0.5 mg/kg cabergoline i.p., once daily for 7 days. On the 8th day, rats in each treatment group received a challenge dose of 0.05 mg/kg apomorphine or saline s.c. The temporal changes in the number of rotations away from the 6-OHDA lesion side were evaluated after the challenge. The apomorphine challenge increased the number of rotations more markedly in the apomorphine pretreated rats than in the other pretreatment groups. In cabergoline pretreated rats, the number of rotations was significantly lower than that of saline-pretreated animals. Pretreatment with saline did not alter the apomorphine sensitivity of rotational behavior. These findings suggest that the repeated administration of long-acting dopamine agonists may reduce sensitized dopaminergic transmission in dopamine-depleted rats, whereas short-acting ones may further enhance sensitization of the transmission process.     

Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats

We explored the impact of exposure to an obesogenic diet (High Fat–High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10 days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10 days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed.     

Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment

Recent reports suggest the involvement of free radicals in the pathophysiology of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brain is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energy metabolism, it is not known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are associated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340 g] were injected with intracerebroventricular STZ [3 mg/kg] bilaterally stereotaxically under ketamine anesthesia [70 mg/kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learning and memory behavior was analyzed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The behavioral tests were performed on day 17, 18 and 19. The rats developed significant deficits in learning, memory and cognitive behavior, indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development of oxidative stress in the brain as indicated by significant elevations in malondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dementia.     

Protracted Effects of Juvenile Stressor Exposure Are Mitigated by Access to Palatable Food

Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM), social interaction and forced swim test (FST). Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD) 27–29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity.     

Tachykinin Systems in the Spinal Cord and Basal Ganglia: Influence of Neonatal Capsaicin Treatment or Dopaminergic Intervention on Levels of Peptides, Substance P–Encoding mRNAs, and Substance P Receptor mRNA

The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of small doses human interferon-alpha intranasal injection on behavior of rats of different age

Behavior of young (3-4 month old) and ageing (12-15 month old) rats was studied during chronic intranasal application of low doses (10 ME or 350 ME) of human interferon-alpha (HIA). In ageing rats HIA did not affect dynamics (days 0th, 8th and 16th) of (a) locomotive and (b) investigative activity in the "open field" test and in two-side defensive conditioning, and (c) decreased anxiety ("open field", "light-darkness" test). In young rats HIA (a) increased locomotive activity by 16th day (it decreased in control), (b) investigative activity did not change (in control it decreased by 8th day; "open field" test), (c) anxiety decreased in the "open field" and increased in "light-darkness" tests, (d) development of conditioned reflex improved (during 2nd learning session in 5 days after the first one). Thus, small doses of HIA differently affected behavior of rats depending on the age and experimental situation. However, both HIA doses changed rats' behavior in the same direction. We suggest that chronic low doses of HIA can regulate different aspects of behavior, but not suppress activity as it is commonly thought. This regulation can be performed via modulation of neuro-immuno-endocrine complex.     

Coexistence of Anhedonia and anxiety-independent increased novelty-seeking behavior in the chronic mild stress model of depression

Previous research demonstrated excessive decreases in reward sensitivity and increases in harm avoidance in depressed individuals. These results straightly lead to a hypothesis that depressed patients should avoid novelty or express reduced novelty-seeking behavior. Nevertheless, literature in this regard is inconsistent. Furthermore, whether the potentially altered novelty-associated behavior is dependent on changed anxiety/fear or related to altered goal-directed approaching tendency is unclear. Here, we tested novel object-approaching behavior in a free-exploration paradigm in chronic mild stress (CMS)-induced anhedonic and stress-resistant rats respectively. Other CMS-induced, emotional behaviors were also examined in a battery of behavioral tests including novel cage, exploration, locomotor activity and elevated plus maze (EPM). We found that compared with controls, stress-resistant rats who consistently showed lower anxiety level in EPM (time in open arms) and, open-field (OF) test (time in central area) showed no sign of enhanced novel object approaching behavior. To the contrary, the anhedonic ones who did not express any sign of reduced anxiety showed paradoxically intensified novelty-approaching behavior. We concluded that reduced anxiety would not necessarily lead to enhanced novelty-seeking behavior; anhedonia coexists with anxiety-independent, increased novelty-seeking behavior. The salient paradox of coexistence of anhedonia and increased novelty-seeking behavior was critically discussed.     

The orexin-1 receptor antagonist SB-334867 attenuates anxiety in rats exposed to cat odor but not the elevated plus maze: An investigation of Trial 1 and Trial 2 effects

The orexins are hypothalamic neuropeptides most well known for their roles in regulating feeding and sleeping behaviors. Recent findings suggest that orexin-A may also modulate anxiety, although how and when the orexin system is involved remains unclear. To address this, we investigated the dose-dependent effects of the orexin-1 receptor antagonist SB-334867 in two rodent models of anxiety: the cat odor avoidance model and the elevated plus maze. In both models we tested the effects of SB-334867 when anxiety is novel (Trial 1) and familiar (Trial 2). In the first experiment, Wistar rats were treated with vehicle or SB-334867 (5, 10 or 20 mg/kg, i.p.) prior to their first or second exposure to cat odor. During Trial 1, rats treated with 10 mg/kg of SB-334867 approached the cat odor stimulus more than vehicle-treated rats. During Trial 2 the effects were more marked, with 10 mg/kg of SB-334867 increasing approach times, increasing the number of times rats exited the hide box to engage in exploratory behavior, and decreasing overall hide times. In addition, the 20 mg/kg dose decreased general activity during Trial 2. In the second experiment, the effects of SB-334867 (10 and 20 mg/kg) were tested in the elevated plus maze. There were no significant differences produced by drug treatment during either Trial 1 or Trial 2. Results suggest that SB-334867 decreases anxiety induced by some, but not all, stressors.     

Sex differences and sex hormones in anxiety-like behavior of aging rats

Sex differences in the prevalence of affective disorders might be attributable to different sex hormone milieu. The effects of short-term sex hormone deficiency on behavior, especially on anxiety have been studied in numerous animal experiments, mainly on young adult rats and mice. However, sex differences in aged animals and the effects of long-term hypogonadism are understudied. The aim of our study was to analyze sex differences in anxiety-like behavior in aged rats and to prove whether they can be attributed to endogenous sex hormone production in males. A battery of tests was performed to assess anxiety-like behavior in aged female, male and gonadectomized male rats castrated before puberty. In addition, the aged gonadectomized male rats were treated with a single injection of estradiol or testosterone or supplemented with estradiol for two-weeks. Female rats displayed a less anxious behavior than male rats in most of the conducted behavioral tests except the light-dark box. Long-term androgen deficiency decreased the sex difference in anxiety either partially (open field, PhenoTyper cage) or completely (elevated plus maze). Neither single injection of sex hormones, nor two-week supplementation of estradiol in gonadectomized aged male rats significantly affected their anxiety-like behavior in the elevated plus maze. In conclusion, our results confirm sex differences in anxiety in aged rats likely mediated by endogenous testosterone production in males. Whether long-term supplementation with exogenous sex hormones could affect anxiety-like behavior in elderly individuals remains to be elucidated.     

Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity.

Unilateral injection into the right substantia nigra of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) produces extensive loss of dopaminergic cells ('hemi-parkinsonian rat'). The pineal hormone melatonin, which is a potent antioxidant against different reactive oxygen species and has been reported to be neuroprotective in vivo and in vitro, was evaluated for potential anti-Parkinson effects in this model. Imbalance in dopaminergic innervation between the striata produced by intranigral administration of 6-OHDA results in a postural asymmetry causing rotation away from the nonlesioned side. Melatonin given systemically prevented apomorphine-induced circling behavior in 6-OHDA-lesioned rats. Reduced activity of mitochondrial oxidative phosphorylation enzymes has been suggested in some neurodegenerative diseases; in particular, selective decrease in complex I activity is observed in the substantia nigra of Parkinson's disease patients. Analysis of mitochondrial oxidative phosphorylation enzyme activities in nigral tissue from 6-OHDA-lesioned rats by a novel BN-PAGE histochemical procedure revealed a clear loss of complex I activity, which was protected against in melatonin-treated animals. A good correlation between behavioral parameters and enzymatic (complex I) analysis was observed independent of melatonin administration. A deficit in mitochondrial complex I could conceivably contribute to cell death in parkinsonism via free radical mechanisms, both directly via reactive oxygen species production and by decreased ATP synthesis and energy failure. Melatonin may have potential utility in the treatment of neurodegenerative disorders where oxidative stress is a participant.     

Dopamine-Dependent Postnatal Development of Enkephalin and Tachykinin Neurons of Rat Basal Ganglia

The influence of deprivation of the neurotransmitter dopamine (DA) on the development of [Met5]-enkephalin (ME) and substance P (SP) neuropeptide systems of the striatum was investigated in Sprague-Dawley rats. The neurotoxin 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on postnatal day 3 in rats, and the animals were killed at different postnatal time points until 35 days of age. The levels of ME and SP were determined by radioimmunoassay, and the abundance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA in the striatum was assessed by Northern blot hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT), and their acid metabolites were determined by HPLC with electrochemical detection. The postnatal development of the PPE-derived peptide ME and the PPT-derived peptide SP closely paralleled the appearance of the respective mRNAs coding for these peptides. The dopaminergic lesion with 6-OHDA led to a marked depletion of DA and its metabolites but produced an increase in content of 5-HT and its metabolite in the striatum. The lesion did not affect the ME and PPE mRNA levels in the striatum up to 25 days but increased the levels at 35 days. In contrast, a decreased developmental expression in SP and PPT mRNA was observed throughout the observation period. The lesion failed to influence the development of the mRNA coding for the structural protein beta-actin. The results indicate that the normal development of enkephalin, tachykinin, and 5-HT systems of the striatum is dependent on the availability of DA, the integrity of dopaminergic neurons, or both. The studies provide evidence for an interrelationship and interdependence between the development of neurotransmitter and neuropeptide systems. It is suggested that an early developmental abnormality in the DA system could permanently alter the neuropeptide systems, which in turn could influence the progression and expression of the DA-deficiency state parkinsonism, Lesch-Nyhan disease, or both.     

Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats

Prenatal irradiation is known to have aversive effects on the brain development, manifested in changes in some behavioural parameters in adult individuals. The aim of our work was to assess the effect of prenatal irradiation on different forms of behaviour and on hippocampal neurogenesis in rats. Pregnant female rats were irradiated with a dose of 1 Gy of gamma rays on the 16th day of gravidity. The progeny of irradiated and control animals aged 3 months were tested in Morris water maze (MWM), open field (OF) and in elevated plus maze test (PM). The prenatal irradiation negatively influenced the short-term spatial memory in MWM in female rats, although the long-term memory was not impaired. A statistically significant increase of basic locomotor activity in OF was observed in irradiated rats. The comfort behaviour was not altered. The results of PM showed an increase of anxiety in irradiated females. The level of hippocampal neurogenesis, assessed as the number of cells labelled with 5-bromo-2-deoxyuridine in the area of gyrus dentatus, was not statistically different in irradiated rats. Our results indicate, that prenatal irradiation with a low dose of gamma-rays can affect some innate and learned forms of behaviour in adult rats. We did not confirm a relation of behavioural changes to the changes of hippocampal neurogenesis.     

Effect of 5,6-dihydroxytryptamine and 6-hydroxydopamine on the maze behavior of the snail Helix lucroum

One-trial Y-maze test in snails did not reveal any predominance of the right or left alley choice. The choice of the right alley (but not of the left one) was accompanied by a slowing down of forward motion. After the administration of 10 mg/kg of 6-hydroxydopamine 24 hr before the test, right alley choice without slowing down became more frequent. Administration of 5,6-dihydroxytrypamine (10 mg/kg) caused a reduction of motion rate along all parts of the maze and an increase in frequency of the orienting head movements towards the alley to be chosen.     

Peculiarities of exploration behavior of socially deprived rats in stress situation

Male Wistar rats (n = 18) were studied at the age of 120 days after social deprivation in the period from the 22nd to 70th days of postnatal development. They displayed significant lower activity in the open field, elevated plus-maze, and Porsolt test than control animals (n = 19). Decreased exploratory activity was found to be related with higher level of anxiety. This was confirmed by their avoidance of open arms of the elevated plusmaze and reactions to approaching hand. These animals had problems in the maze arm choice. They showed low time variability of choice-related actions (waiting in the center of the open field or elevated plus-maze and change in the movement direction along an open-field wall, including the movement per se, and arm choice and changing, i.e., alternative choice). Shorter time of choice-related actions was observed in situations of unequal alternatives.     

Spontaneous light or dark preference in albino mice?

The present experiment examined spontaneous visual choice behaviour and acquisition of a positively reinforced visual discrimination task in Swiss albino mice. In experiment I animals were given 4 consecutive trials in which they could freely enter either a dimly illuminated or a darkened arm of a Y-maze; the position of the light stimulus was randomized across trials. D groups and L groups were tested during the dark and the light period of the day respectively. Results revealed a significant spontaneous preference for the illuminated arm of the maze, independent of the testing period. It is suggested that the dim light has a reinforcing value because it provides additional information about a novel environment. In a second experiment an appetitive visual discrimination task was carried out in the same Y-maze. After a pretraining period, half the animals were reinforced in the illuminated arm and half were reinforced in the darkened one, on five consecutive days. On the first test session all groups of animals chose the illuminated arm significantly more frequently, whereas light/dark choices reached chance level on the last test session. Discrimination learning was not acquired and a behavioural analysis revealed an increasing tendency to a side preference across testing.     

Inverse association of high-fat diet preference and anxiety-like behavior: a putative role for urocortin 2

The aim of this study was to investigate whether the preference for a palatable high-fat diet (HFD) is associated with response to novelty and with anxiety-like behavior in rats and whether such fat preference correlates with gene expression of hypothalamic neuropeptides related to feeding. We subjected male rats to two tests of exploration of novel environments: the multivariate concentric square field (MCSF) and the elevated plus maze (EPM). The rats were then exposed to a 5 - day test of preference for a palatable HFD versus reference diets. Messenger RNA (mRNA) levels of 21 neuropeptides were investigated by quantitative polymerase chain reaction. We found a strong positive correlation of HFD preference and open-arm activity in the EPM (% open-arm time, r _s = 0.629, df = 26, P   <   0.001). Thus, HFD preference was inversely associated with anxiety-like behavior. The same association was found for HFD preference and behavior in the MCSF (bridge entries, r _s = 0.399, df = 23, P  = 0.048). In addition, the HFD preference was positively correlated ( r _s = 0.433, df = 25, P  = 0.021) with hypothalamic mRNA levels of urocortin 2 (Ucn 2). Moreover, behavior in the EPM was significantly correlated with expression levels of the receptor for Ucn 2, the corticotropin-releasing factor receptor 2, in the hypothalamus ( r _s = 0.382, df = 33, P  = 0.022, pituitary ( r _s = 0.494, df = 31, P  = 0.004) and amygdala ( r _s = 0.381, df = 30, P  = 0.032). We conclude that preference for palatable HFD is inversely associated with anxiety and propose that Ucn 2 signaling may play a role in this association.     

Prenatal Effect of Fluoxetine on Nociceptive System Reactivity and Psychoemotional Behavior of Young Female and Male Rats

Reactivity of the nociceptive system, psychoemotional behavior and cognitive abilities in female and male rats born to mothers that were exposed to chronic injection of fluoxetine, a serotonin reuptake inhibitor, on days 9–20 of pregnancy were studied in a battery of behavioral tests during the prepubertal period. It was found that chronic injection of physiological saline to pregnant females evoked enhanced nociceptive responses in their offspring of both sexes while fluoxetine injection neutralized the effects of such an invasive intervention, demonstrating thereby the antinociceptive effect of this agent. Negative effects of maternal fluoxetine included a weight loss in the neonate offspring of both sexes and 25-day-old males, as well as the increased anxiety level in females only as detected in the elevated plus maze test. Fluoxetine had no effect on the level of depressive-like behavior in the forced swim test in rats of both sexes. The positive prenatal effect of fluoxetine manifested itself in males as an improved spatial learning ability in the Morris water maze; the anti-nociceptive effect of chronic fluoxetine injection, as compared to the pro-nociceptive effect of chronic saline injection, can also be considered as a positive effect of fluoxetine. Sex differences in the prenatal effect of fluoxetine were revealed in the anxiety level with more anxiety behavior in females.