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The effects of complex motor task learning on subsequent motor performance of adult rats exposed to alcohol on postnatal days 4 through 9 were studied. Male and female Long-Evans rats were assigned to one of three treatments: (1) alcohol exposure (AE) via artificial rearing to 4.5.g kg-1 day-1 of ethanol in a binge-like manner (two consecutive feedings), (2) gastrostomy control (GC) fed isocaloric milk formula via artificial rearing, and (3) suckling control (SC), where pups remained with lactating dams. After completion of the treatments, the pups were fostered back to lactating dams, and after weaning they were raised in standard cages (two-three animals per cage) until they were 6 months old. Rats from each of the postnatal treatments then spent 20 days in one of three conditions: (1) inactive condition (IC), (2) motor control condition (MC) (running on a flat oval track), or (3) rehabilitation condition (RC) (learning to traverse a set of 10 elevated obstacles). After that all the animals were tested on three tasks, sensitive to balance and coordination deficits (parallel bars, rope climbing and traversing a rotating rod). On parallel bars, both male and female rats demonstrated the same pattern of outcomes: AE-IC rats made significantly more mistakes (slips and falls) than IC rats from both control groups. After 20 days of training in the RC condition, there were no differences between AE and both SC and GC animals in their ability to perform on the parallel bars test. On rope climbing, female animals showed a similar pattern of abilities: AE-IC rats were the worst group; exercising did not significantly improve the AE rats' ability to climb, whereas the RC groups (SC, GC and AE) all performed near asymptote and there were no significant differences among three neonatal treatment groups. There was a substantial effect of the male rats' heavier body weight on climbing ability, and this may have prevented the deficits in AE rats behavior from being detected. Nevertheless, male animals from all three postnatal treatments (SC, GC and AE) were significantly better on this task after RC. Female and male rats from all three postnatal groups demonstrated significantly better performance on the rotarod task after 20 days of 'rehabilitation'. These results suggest that complex motor skill learning improves some of the motor performance deficits produced by postnatal exposure to alcohol and can potentially serve as a model for rehabilitative intervention.
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PMID:Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats . I. Behavioral results. 968 83

Dopaminergic projections to the medial prefrontal cortex (mPFC) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) to examine how dopamine (DA) asymmetry in the mPFC influences voluntary ethanol consumption. Differences in nucleus accumbens (NAS) DA neurotransmission have been related to individual differences in locomotor activity and in the rewarding efficacy of ethanol. Therefore, differences in locomotor activity were used to further characterize the effects of unilateral mPFC 6-OHDA lesions on ethanol consumption. Male Long Evans rats were assessed for high versus low levels of spontaneous locomotor activity. DA terminals in the left or right mPFC were unilaterally lesioned with 6-OHDA, resulting in an average DA depletion of 54% and 50%, respectively. After a minimum seven-day recovery period, preference for a 10% ethanol solution vs. water was determined in a 24-h 2-bottle home-cage free-choice paradigm. Left mPFC 6-OHDA lesions increased and right lesions decreased ethanol consumption. These differential effects of left and right lesions were primarily attributable to rats exhibiting low locomotor activity prior to surgery. The present data suggest that right greater than left cortical DA asymmetry in combination with low endogenous NAS DA (predicted by low locomotor activity levels) may increase the vulnerability to abuse ethanol.
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PMID:Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially affect voluntary ethanol consumption. 1009 12

Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict differences in the voluntary consumption of ethanol in male Long-Evans rats. Animals were assessed for their preferred direction of turning behavior and for high vs. low levels of spontaneous locomotor activity, as determined during nocturnal testing in a rotometer. Subsequently, preference for a 10% ethanol solution vs. water was determined in a 24-h two-bottle home-cage free-choice paradigm. Rats exhibiting a right-turning preference consumed more ethanol than rats showing a left-turning preference. While locomotor activity alone did not predict differences in drinking, turning and locomotor activity together predicted differences in ethanol consumption. Low-activity right-turning rats consumed more ethanol than all the other groups of rats. Previous studies from this laboratory have shown that individual differences in turning behavior are accompanied by different asymmetries in dopamine (DA) function in the medial prefrontal cortex (mPFC). Individual differences in locomotor activity are associated with differences in nucleus accumbens (NAS) DA function. The present data suggest that variations in mPFC DA asymmetry and NAS DA function may underlie differences in the voluntary consumption of ethanol.
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PMID:Rotation, locomotor activity and individual differences in voluntary ethanol consumption. 1009 14

As a first step, the present experiment aimed at characterizing learning and memory capabilities, as well as some motor and sensorimotor faculties, in aged (24-26.5 months) Long-Evans female rats. As a second step, a psychopharmacological approach was undertaken in order to examine the sensitivity of aged rats to muscarinic blockade and to cholinomimetic treatments. Young adult (3-5.5 months) and aged rats were tested for beam-walking performance, locomotor activity in the home cage and an open field, and spatial learning/memory performance in a water maze and a radial maze. Spontaneous alternation rates were assessed in a T-maze. Statistical analysis discriminated between aged rats showing moderate impairment (AMI) and those showing severe impairment (ASI) in the water maze test. Beside their different degrees of impairment in the water maze, AMI and ASI rats were similarly (no significant difference) impaired in beam-walking capabilities, home cage activity and radial maze performance. In the spontaneous alternation task aged rats were not impaired and, in the open-field test, AMI rats were hypoactive, but not as much as ASI rats. Neither of the cognitive deficits was correlated with a locomotor or a sensorimotor variable, or with the body weight. When tested in the radial maze, a low dose of scopolamine (0.1 mg/kg i.p.) produced memory impairments which were significant in AMI and ASI rats, but not in young rats. Combined injections of scopolamine and physostigmine (0.05 and 0.1 mg/kg) or tacrine (THA, 3 mg/kg) showed physostigmine (0.1 mg/kg) to compensate for the scopolamine-induced impairments only in AMI rats. whereas THA was efficient in both AMI and ASI rats. The results indicate: (i) that rats with different degrees of spatial memory impairment in the water maze are similarly hypersensitive to muscarinic blockade when tested in a radial maze test; and (ii) that under the influence of a dose of scopolamine which is subamnesic in young rats, aged rats respond to anticholinesterase treatments according to the level of performance achieved in the water maze: moderately impaired rats are sensitive to both physostigmine and THA, whereas more severely impaired rats are sensitive only to THA.
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PMID:Sensitivity to cholinergic drug treatments of aged rats with variable degrees of spatial memory impairment. 1021 May 22

Three-month old Long-Evans female rats were submitted to aspirative lesions of the fimbria-fornix and intrahippocampal grafts of a cell suspension prepared from a region of the fetal brain including the septum and the diagonal band of Broca (rich in cholinergic neurons) or the raphe (rich in serotonergic neurons). A group of lesioned rats was grafted with both suspensions mixed. Lesion-only and sham-operated rats served as controls. Four months after the lesions, all rats were tested daily for locomotor activity in their home cage, 1 day without being injected, 2 days with an injection of NaCl and 5 days with an injection of 1 mg/kg (i.p.) d-amphetamine. The effects of the lesions and grafts were assessed by measuring the accumulation of [3H]-choline or [3H]-5-hydroxytryptamine (5-HT) by hippocampal slices, and the electrically-evoked release of tritium. Amphetamine injections produced hyperlocomotion which was potentiated by the lesion. This lesion-induced potentiation was also found in rats with septal grafts, but not in those with raphe or co-grafts. The uptake and electrically-evoked release of [3H]-acetylcholine or [3H]-5-HT were reduced in hippocampal slices from lesion-only rats. In rats which received grafts of septal cells or co-grafts, but not in those with raphe grafts, uptake and release of [3H]-acetylcholine were close to normal. Uptake and release of [3H]-5-HT were close to normal in rats with raphe grafts or with co-grafts, but not in those with septal grafts. Altogether, these data suggest that damage to the serotonergic afferents of the hippocampus might play some role in the potentiation of amphetamine-induced hyperlocomotion associated with fimbria-fornix lesions.
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PMID:The potentiation of amphetamine-induced hyperlocomotion by fimbria-fornix lesions in rats is abolished by intrahippocampal grafts rich in serotonergic neurons. 1032 73

In prone anesthetized rabbits, we used Evans blue-dyed albumin (EBA) to study regional pleural filtration and FITC dextran to study regional pleural absorption. Evans blue was injected intravenously, and the animals were ventilated for 6 h at either of two levels of ventilation. Postmortem the right rib cage was frozen and thawed before study. EBA fluorescence emitted from the rib cage surface was measured along the cranial-caudal axis near the mid chest with fluorescence videomicroscopy. Fluorescent light intensity increased from the third to the eighth rib in a cyclic fashion, with peaks at the ribs and troughs at the intercostal spaces. This increase was greater at the higher ventilation. Fluorescent images of cross sections of a frozen rib cage verified a cranial-caudal gradient in filtration. Fluorescent images of FITC dextran absorbed from the pleural space into the rib cage surface indicated major areas of absorption at the ventral, caudal, and cranial regions adjacent to the lung margins and areas of absorption scattered in the intercostal spaces. Simultaneous measurements of EBA filtration and FITC absorption showed sites of maximal filtration that were different from sites of maximal absorption. Pleural uptake of fluorescent microspheres (2-microm diameter) located lymphatic stomata distributed randomly within clusters in the intercostal spaces and channels of lymphatic lacunae parallel to blood vessels. Diaphragmatic uptake of microspheres was confined mainly to the ventral surface of the central tendon. Visceral pleural absorption was minimal.
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PMID:Regional pleural filtration and absorption measured by fluorescent tracers in rabbits. 1046 21

This study extended to treadmill exercise training our prior report (Dishman RK, Warren JM, Youngstedt SD, Yoo H, Bunnell BN, Mougey EH, Meyerhoff JL, Jaso-Friedmann L, and Evans DL. J Appl Physiol 78: 1547-1554, 1995) that activity wheel running abolished the suppression of footshock-induced natural killer (NK) cell cytolysis. Twenty-four male Fischer 344 rats were assigned to one of three groups (n = 8, all groups): 1) a home-cage control group, 2) a sedentary treatment group, or 3) a treadmill-running group (0 degrees incline, 25 m/min, 35 min/day, 6 days/wk). After 6 wk, the treadmill and sedentary groups received 2 days of footshock. Splenic NK cytotoxicity was determined by standard 4-h (51)Cr release assay. Percentages of lymphocytes were determined by flow cytometry. Plasma levels of ACTH, corticosterone, and prolactin concentration were measured by radioimmunoassay. After footshock, percentage of lysis relative to home-cage controls was 40% and 80% for sedentary and treadmill-trained animals, respectively (P < 0.05). Our results indicate that the protective effect of chronic exercise on innate cellular immunity in the Fischer 344 male rat is not restricted to activity wheel running, nor is it explained by elevations in basal NK activity, increased percentages of splenic NK and cytotoxic T cells, or increased plasma levels of ACTH, corticosterone, and prolactin.
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PMID:Treadmill exercise training blunts suppression of splenic natural killer cell cytolysis after footshock. 1084 33

The locomotor effects of acute amphetamine treatment (1 mg/kg, i.p.) were assessed in Long-Evans rats after 5,7-dihydroxytryptamine (5, 7-DHT) injections into the fimbria-fornix/cingular bundle (FiFx/CB; 4 microg/side), or the dorsal and median raphe (Raphe; 10 microg). In control rats, amphetamine induced a significant increase of home-cage activity for about 2 h. This effect was similar in Raphe rats, but was absent in FiFx/CB rats. The raphe lesions reduced serotonin concentrations by 50% in the dorsal hippocampus, 75% in the ventral hippocampus and 58% in the fronto-parietal cortex. After FiFx/CB lesions, the reduction amounted 50, 61 and only 25%, in each of these regions, respectively. In the fronto-partietal cortex, dopamine concentration was significantly decreased in Raphe (-27%) and FiFx/CB rats (-65%). The results suggest that a serotonergic denervation of the hippocampus by injections of 5,7-DHT into the FiFx/CB pathways hampers the stimulating effects of amphetamine on locomotor activity. This effect might be related to the reduced dopaminergic tone in the fronto-parietal cortex.
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PMID:When injected into the fimbria-fornix/cingular bundle, not in the raphe, 5,7-dihydroxytryptamine prevents amphetamine-induced hyperlocomotion. 1099 62

At 21 days of age, gonadally intact male Long Evans rats were weaned and placed into standard laboratory conditions (three per cage) or housed singly. They were tested for noncontact erections and sexual performance at 90 and 220 days of age. Rats raised in isolation displayed significantly fewer noncontact erections in response to sensory cues from an estrous female and fewer intromissions when allowed to mate with a female than did males raised in groups. The volume of the posterodorsal component of the medial amygdala (MePD) and the size of neurons within the MePD were significantly smaller in the isolated males than in socially housed males. Similarly, neurons in the sexually dimorphic nucleus of the preoptic area (SDN-POA) were smaller in isolate animals than in controls. As both MePD volume and SDN-POA soma size are responsive to sex steroids, these differences could result if the isolates experienced lower testosterone levels. Finally, the volume of the overall medial amygdala (MeA) correlated significantly with the number of noncontact erections, a relationship that was not explained by housing condition. These findings highlight the role of social experience as a factor in the sexual differentiation of the brain and suggest a positive relationship between the volume of a brain structure and the display of sexual behaviors.
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PMID:Post-weaning social isolation of male rats reduces the volume of the medial amygdala and leads to deficits in adult sexual behavior. 1109 63

Conditioned stimuli (CS) can be devalued by exposure to those stimuli in the absence of primary reward. We tested the hypothesis that dopamine (DA) mediates the control of behavior by conditioned appetitive stimuli. Long-Evans rats were trained to respond for sucrose under a heterogeneous chain schedule in which seeking responses (lever press) turned on a houselight [variable interval (VI)-120 s]; taking responses (wheel turn or chain pull) in the presence of the houselight were reinforced [fixed ratio (FR)-1] by a sucrose pellet. When responding on this schedule was stable, the levers were retracted and subjects had access to the sucrose-taking manipulandum only. Sucrose-taking responses were either extinguished or reinforced under the influence of the DA antagonist, pimozide. Control groups were also reinforced for sucrose-taking responses but received no injection or a vehicle injection prior to each session. Responses of extinction and pimozide-treated groups declined over sessions. Sucrose-seeking responses were measured in a later test when subjects had no access to the sucrose-taking manipulandum or to the reinforcer. Both extinction and pimozide manipulations reduced seeking responses, relative to the respective control groups. Pimozide injections in the home cage had no effect. These data support the idea that DA mediates the conditioned reinforcing properties provided by access to the taking link of the chain.
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PMID:Pimozide, like extinction, devalues stimuli associated with sucrose taking. 1132 15


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