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A J Nonneman

Publications and source records attributed to A J Nonneman.

At least 19 recordsLinked to original sources
PubMed1993

Behavioral effects of selective and nonselective dopamine agonists on young rats after irreversible antagonism of D1 and/or D2 receptors.

In general, preweanling and adult rats respond similarly when challenged with competitive dopamine (DA) agonists or antagonists. In contrast, results using a noncompetitive antagonist suggest that the D1 and D2 receptor systems of preweanling and adult rats differ in some critical way. To further assess this phenomenon, the behavioral effects of irreversible receptor blockade were assessed across 8 days in NPA (a nonselective DA agonist), quinpirole (a D2 agonist), or SKF 38393 (a D1 agonist) treated 17-day-old rat pups. The irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) did not block the locomotor activity and rearing of NPA- or quinpirole-treated rat pups, nor did EEDQ reduce SKF 38393-induced grooming. Moreover, pretreatment with EEDQ appeared to potentiate the normal increases in locomotor activity and rearing produced by NPA, but only when D2 receptors were not protected by a previous injection of sulpiride (a D2 antagonist). Taken together, these results are consistent with the presence of large reserves of D1 and D2 receptors in the preweanling rat pup.

Aging↗
PubMed1992

Effects of irreversible dopamine receptor inactivation on locomotor activity and grooming in the 17- and 90-day-old rat.

Ontogenetic differences in the behavioral recovery of R(-)-propylnorapomorphine (NPA) treated rats were assessed following irreversible DA receptor antagonism by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). In the first two experiments, 17- and 90-day-old rats were given EEDQ (7.5 or 15.0 mg/kg, IP) or vehicle after half the rats were initially treated with the selective DA D-1 and D-2 antagonists SCH 23390 and sulpiride. (The sulpiride/SCH 23390 treatment protects DA receptors from EEDQ-induced inactivation.) NPA's (0.1 or 1.0 mg/kg) effects on locomotor activity and grooming were assessed 1, 2, 4 and 8 days after the EEDQ pretreatment. In a third experiment, the effects of habituating the 17- and 90-day-old rats to the testing chamber were assessed 1, 2 and 4 days after EEDQ pretreatment. In this experiment, some groups received successive treatments of saline or NPA prior to behavioral testing. To assess the possible effects of drug-sensitization other groups received saline on days 1 and 2 and NPA on day 4. In 90-day-old rats, EEDQ eliminated, for up to 4 days, the ability of NPA to enhance locomotor activity and depress grooming. Prior treatment with DA antagonist drugs was sufficient to protect DA receptors from EEDQ-induced inactivation, since these groups exhibited normal behavioral responses after challenge with NPA. In contrast, EEDQ did not eliminate, and may have enhanced, NPA's effect on the locomotor activity and grooming of 17-day-old rat pups. Habituating the rats to the testing chamber decreased the locomotor activity of the mature rats, but not the 17-day-old rat pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Reinforced responding of the 11-day-old rat pup: synergistic interaction of D1 and D2 dopamine receptors.

Reinforced responding of 11-day-old rat pups was assessed after blockade of D1 and D2 dopamine receptors. Initially, rat pups were trained to traverse a straight alley for nipple attachment reward. Rat pups were than injected IP with either the D1 antagonist SCH 23390 (0.01, 0.015, 0.03, or 0.1 mg/kg), the D2 antagonist sulpiride (15 or 50 mg/kg), or a combination of SCH 23390 (0.015 mg/kg) and sulpiride (15 mg/kg). The approach performance of drug-treated pups was then compared to vehicle-treated pups on both reinforcement and extinction trials. Sulpiride (15 mg/kg) did not affect either the extinction or reinforced responding of 11-day-old rat pups. In contrast, SCH 23390-treated pups showed significantly longer response latencies than the vehicle controls in both extinction and reinforcement conditions. Combined treatment with SCH 23390 and sulpiride produced the longest response latencies. Analyses of "best score" and frequency data indicated that the drug-induced decline in responding was due to effects on both reward processes and motor capability. The combined results indicate that D1 and D2 receptors interact complexly to affect reinforced responding.

Animals↗
PubMed1992

Effects of transplantation of fetal hippocampal or hindbrain tissue into the brains of adult rats with hippocampal lesions on water maze acquisition.

Rats were given bilateral aspiration lesions of the hippocampus. Some of these rats then received bilateral transplants of fetal hippocampal or dorsal ventricular ridge tissue that was dissected from embryonic rat brains at 16 or 17 days of gestation. The remaining rats with hippocampal lesions did not receive fetal brain transplants. Rats with neocortical aspiration lesions, but without transplants, and rats without brain damage were also included in the study. All of the rats were trained to find a submerged platform in a Morris water maze. Rats with the fetal brain transplants were more impaired in some measures of maze learning than were rats with hippocampal lesions only. The results indicate that transplants of fetal brain tissue are not always associated with recovery of behavioral function after brain damage and may even increase a lesion-induced behavioral impairment in tasks that require complex cognitive functioning.

Animals↗
PubMed1991

Effects of SCH 23390 and sulpiride on the reinforced responding of the young rat.

Reinforced responding of 17-day-old rat pups was assessed after blockade of dopamine D1 and D2 receptor systems. Rat pups were trained to traverse a straight alley for nipple attachment reward and then injected with various doses of either sulpiride (D2 antagonist), SCH 23390 (D1 antagonist), or a combination of sulpiride and SCH 23390. The approach performance of drug-treated pups was then compared with vehicle-treated pups on both reinforcement and extinction trials. SCH 23390, but not sulpiride, depressed the appetitive approach responding of the pups. During extinction testing, SCH 23390-treated pups had longer response latencies than pups given vehicle. "Best score" data suggested that SCH 23390 primarily affected reward processes and not motor capability. Most important, the effects of SCH 23390 on reinforced responding were potentiated by sulpiride, suggesting that both the D1 and D2 receptor systems are involved in reward processes.

Age Factors↗
PubMed1991

Anatomical and behavioral sequelae of fetal brain transplants in rats with trimethyltin-induced neurodegeneration.

The effect of transplants of either fetal hippocampal or dorsal ventricular ridge (DVR) tissue into the brains of adult male rats exposed to TMT was determined for two behavioral tasks. Administration of TMT produced deficits in acquisition and performance of an operant differential reinforcement of low response rates (DRL) schedule and learning in the Morris water maze. The fetal transplants developed well within the TMT-damaged brains of the adult rats and numerous axons could be shown to cross the host-transplant interface. The transplants significantly reduced the DRL deficit produced by exposure to TMT. However, the TMT-induced deficit in water maze acquisition was made significantly worse by the hippocampal transplants. The improvement in DRL performance is attributed to the effect on the host brain of an unidentified trophic substance produced by the transplants. However, this positive effect may not protect the brain sufficiently to produce recovery in tasks demanding more complex neural computations than are required to withhold lever-press responses. The transplant-induced deficit observed in some aspects of water maze acquisition and performance may be attributable to either a tumor-like deleterious effect of the mass of the transplant or to abnormal neuronal activity transmitted from the transplant to the host brain. The results of the present study, and those from other similar studies, suggest that transplants of fetal tissue may be useful in producing changes in the brain of an animal exposed to an environmental neurotoxin, but that research should be focused upon development of transplant methodology that will minimize adverse effects of the grafts.

Animals↗
PubMed1990

Ontogeny of locomotor activity and grooming in the young rat: role of dopamine D1 and D2 receptors.

Locomotor activity and grooming were assessed in 11- and 17-day-old rat pups after treatment with selective dopamine (DA) D-1 and D-2 agonists (SKF 38393 and quinpirole, respectively) and antagonists (SCH 23390 and sulpiride, respectively). Quinpirole enhanced the locomotor activity of both the 11- and 17-day-olds, effects antagonized by either SCH 23390 or sulpiride. Drug-induced increases in grooming were apparent only after high doses (30.0 mg/kg i.p.) of SKF 38393 (11- and 17-day-olds) or when SKF 38393 (15.0 mg/kg i.p.) was given in conjunction with sulpiride (11-day-olds). In general, these results suggest that challenge with selective DA agonists and antagonists induces patterns of responding which are similar to those typically observed in adult rats. Moreover, these results indicate that rat pups, like adults, require a functioning DA D-1 receptor system for the expression of DA D-2-mediated activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Effect of forebrain dopamine depletion on novelty-induced place preference behavior in rats.

Novelty-induced place preference behavior of rats was studied in two experiments. In the first experiment, separate groups of animals were habituated to a distinct environment 30 min daily for either zero, one, two, four or eight days. On the day following the last habituation day, animals were allowed 15 min free access to both the habituated (familiar) and a distinct novel environment. The results revealed a significant novelty preference in the two-, four- and eight-day habituation groups. In these same animals, the rate of horizontal and vertical activity was lower in the novel environment relative to the familiar environment. The influence of forebrain dopamine (DA) projections on novelty preference behavior was studied in the second experiment. Animals were given an injection of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens or were given sham surgery, and then they were given four habituation days to one environment. Novelty-induced place preference was blocked in the lesioned animals, as the amount of time spent in the novel and familiar environments was not significantly different. Lesioned animals also failed to show a difference in locomotor activity between the novel and familiar environments. Subsequent assay data revealed that the 6-OHDA lesion reduced DA levels in the nucleus accumbens, anterior striatum and olfactory tubercles by over 65% as compared to sham surgery. These results suggest that novelty preference behavior may be mediated by a central DA pathway similar to that involved in other types of reinforcing stimuli, such as food, water and drugs of abuse.

Animals↗
PubMed1989

Dopamine D-2 receptor mediation of response suppression learning of young rats.

In three experiments, the effects of augmenting or blocking dopamine (DA) D-2 receptor activity on the ontogeny of response suppression learning of preweanling rat pups were determined. In the initial experiment, rat pups were trained to traverse a straight alley for nipple attachment to an anesthetized dam. When footshock (0.2 mA, 0.5 sec) was made contingent on responding, younger (11- and 13-day-olds) rat pups were deficient to older (17- and 19-day-olds) pups at withholding punished responding. In the subsequent experiments, response suppression learning was assessed after injecting 11- and 17-day-old rat pups with the specific DA D-2 agonist, LY 171555 (0.005-, 0.01-, and 0.1-mg/kg, i.p.), or the specific DA D-2 antagonist, sulpiride (5.0-, 15.0-, and 50.0-mg/kg, i.p.). LY 171555 enhanced the punished responding of both the 11- and 17-day-old rat pups; whereas, sulpiride increased the punished responding of the 17-, but not the 11-day-olds. In four additional experiments, the effects of LY 171555 and sulpiride on the locomotor activity, nociception, and reinforcement processes of 17-day-old rat pups was assessed. Rat pups given LY 171555 (0.01 mg/kg, i.p.) exhibited enhanced locomotor activity and a trend towards hyperanalgesia using a hot plate task. Sulpiride (15.0 mg/kg, i.p.) completely antagonized LY 171555's activity enhancing effects and had hyperalgesic properties. In two experiments, sulpiride did not affect the nonpunished appetitive responding of the 17-day-olds; whereas, haloperidol-treated pups responded on fewer reinforced trials than did saline-treated pups. Therefore, these results indicate that the response suppression learning of 17-day-old rat pups is mediated, at least partially, by a DAD-2 receptor system, and that D-2 receptors are also involved in the locomotor activity and nociceptive responses of young rat pups.

Animals↗
PubMed1989

Prefrontal cortex lesions differentially disrupt cocaine-reinforced conditioned place preference but not conditioned taste aversion.

The reinforcing efficacy of cocaine is thought to involve, at least in part, mesocortical dopaminergic (DA) neurons. Rats will self-administer cocaine applied directly into the medial prefrontal cortex but not into nucleus accumbens or the ventral tegmental area (Goeders & Smith, 1983). The present experiments were conducted to assess whether lesions of prefrontal cortex (mesocortical DA target regions) attenuate the reinforcing properties of systemically administered cocaine. Male Sprague-Dawley rats were anesthetized, and one of three subfields (medial, orbital, or precentral) of the prefrontal cortex was removed by aspiration or no brain injury was done (sham operates). In four experiments the rats were tested on conditioned place preference (CPP), conditioned taste aversion (saccharin conditioned stimulus, cocaine unconditioned stimulus), general activity in the running wheel and open field, and food-reinforced spatial alternation in the T-maze. Sham operates demonstrated a cocaine-induced place preference, rats with medial frontal lesions showed a cocaine-induced place aversion, and other operates showed neither a conditioned place preference nor an aversion. The results of this experiment suggest that lesions of the DA projection fields of the prefrontal cortex in the rat reduce the positive reinforcing properties of systemically injected cocaine. In the second experiment, all subjects showed a conditioned taste aversion of equal magnitude. This suggests that whereas the positive reinforcing properties were affected differentially by prefrontal cortex lesions, the aversive properties were not affected. In Experiment 3 there were no lesion-induced differences in activity in either the running wheel or the open field. Therefore, changes in motor activity cannot account for the CPP data. In the final experiment, the medial frontal operates were impaired relative to the precentral and sham operates on learning to alternate choices in the T-maze, but the orbital frontal operates' performance was not different from that of any other group. This suggests that a general disruption of all reinforcement mechanisms did not occur following these lesions. Instead, these results indicate that mesocortical DA projection regions are involved with mediating the reinforcing properties of cocaine and that there is a separate system mediating the aversive properties of cocaine.

Animals↗
PubMed1988

Constraints on water maze spatial learning in rats: implications for behavioral studies of brain damage and recovery of function.

In an effort to develop spatial learning tasks not requiring food or water deprivation for use in studies of recovery of function after brain damage, T-maze spatial alternation learning was examined in intact rats using water maze swim-escape procedures. Consistent with previous studies, rewarded spatial alternation involving food or water deprivation was readily learned by intact rats. However, none of the groups of rats trained in the swim-escape tasks learned to alternate goal arm choices in the water maze at reliable rates. This was true regardless of whether non-correction or correction procedures were used, and regardless of intertrial delay intervals. Although average alternation rates over sessions did increase from chance levels, the majority of the rats did not reach criterion levels, even with as many as 38 consecutive days of testing. In contrast, a conditional spatial alternation task in the water maze, using a win-shift procedure, was readily learned. Surprisingly, a win-stay version of this conditional spatial task was not learned over 21 days of testing. These unexpected constraints on spatial learning and memory processes in rats cannot be attributed simply to failure of spatial information processing, nor to strict limitations on working memory in swim-escape tasks, since excellent spatial navigation abilities have been documented, and mastery of at least some working-memory tasks have now been demonstrated in swim-escape tasks.

Animals↗
PubMed1986

Perinatal glucocorticoids disrupt learning: a sexually dimorphic response.

Glucocorticoid hormones administered during the perinatal period transiently inhibit postnatal granule cell neurogenesis, and thus interfere with normal hippocampal-dentate gyrus development. Chronic deficits on behavioral tests sensitive to hippocampal-dentate function result from such treatments. In the present study rats of both sexes received either a high dose (100 mg/kg) or low dose (1 mg/kg) of dexamethasone (a synthetic glucocorticoid) on postnatal day four. Control subjects received saline or nutritional deprivation intended to produce body and brain growth suppression comparable to that observed in low dose subjects. Behavioral tests sensitive to cerebellar (motor coordination) and hippocampal (place response acquisition and reversals) dysfunction were conducted in adulthood. Control and nutritional control subjects did not differ from each other on any behavioral measures. Motor coordination tests revealed no evidence of chronic dysfunction in dexamethasone treated or nutritionally deprived subjects. Spatial learning and reversal tests revealed a gender and dose-response effect for dexamethasone treatment. Low dose subjects were impaired relative to controls. High dose subjects exhibited significant learning impairments relative to low dose and saline or nutritional control subjects. Within the high dose group only, female subjects were more impaired than male subjects. These gender dependent effects may be related to enhanced glucocorticoid binding in the hippocampi of female versus male rats.

Animals↗
PubMed1986

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.

Animals↗
PubMed1985

Perinatal glucocorticoids alter dentate gyrus electrophysiology.

Perinatal glucocorticoid administration produces permanent spatial discrimination learning deficits in rats, presumably referable to changes in the development of neural systems subserving such functions. Because the hippocampal dentate gyrus and its afferent/efferent circuitry appear selectively vulnerable to neonatal steroid treatments, we have examined adult rats treated with neonatally administered glucocorticoids using electrophysiological methods. The techniques were chosen to reveal the topographic and neurophysiologic responsiveness of the major afferent supply to the dentate gyrus. Rats of both sexes received either a high dose (100 mg/kg) or low dose (1 mg/kg) of the synthetic glucocorticoid dexamethasone on postnatal day four, with control subjects receiving an injection of saline. These dosages have been shown to disrupt hippocampal dependent learning [6,38]. Laminar depth profile analyses of entorhinal cortex-dentate gyrus afferents revealed a significant shift in the spatial distribution of evoked extracellular population synaptic potentials (EPSPs) in glucocorticoid treated subjects. Stimulus-response functions also differed between glucocorticoid treated and control subjects. While response amplitudes at threshold stimulus intensities did not differ between groups, at higher stimulus intensities population spike potentials and associated EPSPs differed in glucocorticoid versus control subjects.

Animals↗
PubMed1984

Role of the caudate nucleus in recovery from neonatal mediofrontal cortex lesions in the rat.

Ablation of medial prefrontal cortex impairs spatial discrimination learning in adult but not in neonatally lesioned rats. Orbital prefrontal cortex and adjacent convexity neocortex need not be left intact to observe this sparing of function. This study examined the possibility that the caudate nucleus, remaining intact after early medial prefrontal cortex lesions, might be involved in the observed behavioral sparing. Neonatal rats given combined lesions of the medial prefrontal cortex and head of the caudate nucleus were compared to age/litter-matched sham-operated controls on spatial alternation and place response acquisition and "reversal" tests. The results show that the performance of these neonatally lesioned subjects was deficient on both tests. The discussion centers on possible recovery mechanisms in rats given prefrontothalamic system damage early in life.

Animals↗