Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.

Assessed the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. NA depletions were achieved through 2 pharmacological means: systemic N-2 chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine (6-OHDA). Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Exp 1, DSP4 and Exp 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the 2 stimuli (a taste cue or a tongue-tactile cue) initially was used as the conditioned stimulus/stimuli (CS) (the stimulus first followed by contingent administration of lithium chloride and later, by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Behavioral effects of neurotoxic lesions of the ascending monoamine pathways in the rat brain.

Intracranial microinjections of 6-hydroxydopamine or 5,6-dihydroxytryptamine into 6 ascending monoamine pathways produced the expected patterns of depletion of telencephalic serotonin, dopamine (DA), and norepinephrine (NE). Serotonin level was specifically lowered after dorsal or median raphe lesions but not after mesolimbic or nigrostriatal system lesions which lowered both NE and DA. Lesions in the locus coeruleus (LC) or ventral noradrenergic bundle lowered only NE, and LC lesions elevated serotonin level. Behavior was examined in an open field, 1-way active avoidance, and 2 passive avoidance (PA) tasks, and measures were taken of water consumption and body weight. Dorsal raphe lesions had no effect on any of the measures; the other 5 lesion groups exhibited deficient acquisition of the 1-way active avoidance task. In the appetitive PA task, only the substantia nigra lesion group exhibited a deficiency. In the step-through PA task, both the substantia nigra and the median raphe groups exhibited a deficit, with the median raphe group exhibiting hyperactivity in the start box during testing. Water consumption was decreased by lesions in the ventral noradrenergic bundle during the 1st postoperative week and was increased in the median raphe group by the 4th postoperative week. Lastly, lesions in the LC dramatically decreased activity in the open field. Results are discussed in regard to the search for specificity of behavioral functions of the distinct ascending monoamine pathways. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of lesions to noradrenergic projections from the locus coeruleus and lateral tegmental cell groups on conditioned taste aversion in the rat.

Lesions of the coeruleo-cortical noradrenergic projections caused marked cortical noradrenaline depletions but were not associated with deficits in the acquisition or extinction of a conditioned taste aversion (CTA). Lesions of lateral tegmental noradrenergic projections resulted in marked hypothalamic noradrenaline depletions, enhanced neophobia to the novel taste of saccharine, unimpaired acquisition but prolonged extinction of the CTA. However, when animals with lateral tegmental noradrenergic lesions received extensive preconditioning exposure to saccharine, acquisition of the CTA was attenuated and extinction was more rapid than in controls. Alterations in CTA learning and extinction following lesions of the lateral tegmental noradrenergic system appear to reflect alterations in the way that animals with lesions react toward the hedonic aspects of taste-related stimuli rather than alterations in associational or attentional mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats.

The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of differential hippocampal lesions and pre- and postoperative training on extinction.

Examined resistance to extinction of a food-motivated response in a total of 78 male albino Wistar rats with sham operations or bilateral dorsal hippocampal, ventral hippocampal, or combined dorsal and ventral hippocampal lesions in 2 experiments. Surgery occurred either before or after acquisition of the to-be-extinguished response. Ss with combined hippocampal lesions showed greater resistance to extinction than controls if acquisition occurred preoperatively, but less resistance if acquisition occurred postoperatively. Ss with ventral hippocampal lesions were affected in a similar manner but to a lesser degree by differential prior experience. In contrast, dorsal hippocampal-lesioned Ss exhibited no change in approach latency during extinction, irrespective of the timing of surgery. It is suggested that both ventral and combined hippocampal lesions interfere with the changing of an established approach "set." (French summary) (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapeutic effects of HS-3, HS-6, benactyzine, and atropine in soman poisoning of dogs

Rats with intracranial self-stimulation (ICSS) electrodes in the locus coeruleus and adjacent pontine tegmental structures received stereotaxically placed bilateral injections of 6-hydroxydopamine (4 mug/2 mul) into the mesencephalic trajectory of the dorsal tegmental noradrenergic bundle. The consequent depletions of norepinephrine in the cerebral cortices and hippocampi (96.7%) did not result in significant changes in ICSS. Thus, diencephalic and telencephalic noradrenergic projections of the locus coeruleus do not appear to be critical for the occurrence of ICSS from that nucleus or its surrounding region. Nor do these projections appear to be crucially involved in the enhancement of this ICSS by D-amphetamine. Rats in this study showed two-fold increases in responding following injections of D-amphetamine sulfate (0.5 mg/kg) both before and after the lesions of the dorsal tegmental bundle. These results suggest that the ascending projections of the locus coeruleus are not critically involved in ICSS of the dorsal pontine tegmentum.     

Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.     

Deficits in conditioned avoidance responding following adrenalectomy and central norepinephrine depletion are dependent on postsurgical recovery period and phase of the diurnal cycle.

Four experiments with 284 Wistar rats showed that Ss who had undergone combined dorsal noradrenergic bundle lesion (DNBL) and bilateral adrenalectomy were impaired in acquiring a conditioned avoidance response when tested 1 wk following surgery. Normal acquisition was observed, however, when testing occurred 3 wks or more after surgery, despite low levels of both plasma corticosterone and brain norepinephrine. Neither neonatal systemic administration of 6-hydroxy-dopamine to deplete forebrain norepinephrine, combined with the corticosterone inhibitor metyrapone, nor the pharmacological blockade of noradrenergic receptors, combined with adrenalectomy, disrupted acquisition of the avoidance response. Thus, the combination of forebrain norepinephrine loss and low plasma corticosterone did not inevitably impair avoidance acquisition; rather, the determining factor for such impairment was the interval between surgery and testing. The impairment at 1 wk following DNBL and adrenalectomy occurred only for Ss tested during the dark phase of their light cycle. The DNBL abolished the effect of the light–dark cycle on posttraining plasma corticosterone. Findings demonstrate the importance of the phase of diurnal rhythm on both the hormonal and the behavioral effects of altering the pituitary-adrenal axis and/or forebrain norepinephrine. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central noradrenergic neurons: Differential effects on body weight of electrolytic and 6-hydroxydopamine lesions in rats.

Compared the effects of bilateral electrolytic and 6-hydroxydopamine (6-OHDA) lesions of the ventral noradrenergic bundle (VB) in 2 experiments with a total of 67 female albino rats. When Ss were fed only a standard laboratory diet, no significant differences were found between groups. When a high-fat diet supplement was introduced, the group with electrolytic lesions became significantly heavier than the control group; however, the 6-OHDA group did not differ from the controls. Norepinephrine depletion was significantly greater following the 6-OHDA than the electrolytic lesions. Both lesions reduced telencephalic dopamine and serotonin only slightly. Exp II, in which both types of lesions were placed at a rostral ventromedial hypothalamic site, yielded the same pattern of results. Diet-dependent increased in body weight were attributed to the destruction of a non-noradrenergic system, which was spared by the relatively selective 6-OHDA lesion but damaged by the nonselective electrolytic lesion. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dorsal tegmental noradrenergic projection: An analysis of its role in maze learning.

Evaluated the hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning. Four experiments were conducted with 61 male Wistar rats. Maze performance was studied in Ss receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a 'T'-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Ss with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Noradrenaline and partial reinforcement in rats.

Lesions of the dorsal noradrenergic bundle produced by 6-hydroxydopamine, which depleted telencephalic noradrenaline by over 95%, were found to produce resistance to extinction in male albino Wistar rats trained on a continuously reinforced schedule for food reward but not to alter the extinction rate after partial reinforcement training. These results confirm the dorsal bundle extinction effect reported previously (S. T. Mason and S. D. Iversen, 1977) but suggest that it is confined to continuously reinforced situations. The pattern of results is consistent with a role for the dorsal bundle in attentional processes but appears to contradict the predictions required if the dorsal bundle were to have a role in frustrative nonreward. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating context and space within the hippocampus: Effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning.

Rats with complete excitotoxic hippocampal lesions or selective damage to the dorsal or ventral hippocampus were compared with controls on measures of contextually conditioned freezing in a signaled shock procedure and on a spatial water-maze task. Complete and ventral lesions produced equivalent, significant anterograde deficits in conditioned freezing relative to both dorsal lesions and controls. Complete hippocampal lesions impaired water-maze performance; in contrast, ventral lesions improved performance relative to the dorsal group, which was itself unexpectedly unimpaired relative to controls. Thus, the partial lesion effects seen in the 2 tasks never resembled each other. Anterograde impairments in contextual freezing and spatial learning do not share a common underlying neural basis; complete and ventral lesions may induce anterograde contextual freezing impairments by enhancing locomotor activity under conditions of mild stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual modulation of conditioned responses: Role of the ventral subiculum and nucleus accumbens.

The performance of conditioned responses (CRs) is diminished when trained subjects are tested in a novel context. This study tested the hypothesis that the flow of contextual information along the disynaptic "ESA" (entorhinal cortex-ventral subiculum-nucleus accumbens) pathway is responsible for context-related modulation of CRs. Rabbits received electrolytic or sham lesions of the ventral subiculum followed by discriminative avoidance conditioning and counterbalanced extinction sessions in the original training context, a novel context, and the original training context with a novel cue. Neuronal activity was recorded simultaneously in the nucleus accumbens, cingulate cortex, and basolateral amygdala. The lesions did not affect the acquisition of avoidance behavior or prevent the reduction of CRs in response to a novel cue. However, the lesions did reduce CR incidence during extinction, and they did eliminate a further novel-context-induced CR reduction found in controls. In addition, lesions disrupted context-dependent neuronal responses in the nucleus accumbens but not in the cingulate cortex or amygdala. These findings are interpreted as supportive of the hypothesis that the ESA pathway mediates contextual modulation of CRs during extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal stimulation on acquisition, extinction, and generalization of conditioned suppression in the rat.

In 6 experiments, a total of 142 male Holtzman rats implanted with electrodes in the dorsal or ventral hippocampus received posttrial stimulation in training sessions with footshock reinforcement. Afterdischarges without overt seizures were consistently without effect on the rate of acquisition of suppression of licking during an auditory CS, although conditioning was retarded by the delivery of distracting stimuli following footshock. The rate of conditioning remained insensitive to elicitation of dorsal hippocampal afterdischarges (DHAD) despite subsequent alterations of session length, intertrial interval, and preexposure to the CS. However, faster extinction of suppression occurred following DHAD, suggesting a limited but essential role of the hippocampus in addressing stored information. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions

The hippocampus plays an essential role in spatial learning. To investigate whether the whole structure is equally important, we compared the effects of variously sized and localized hippocampal aspiration lesions on spatial learning in a Morris water maze. The volume of all hippocampal lesions was determined. Dorsal hippocampal lesions consistently impaired spatial learning more than equally large ventral lesions. The dorsal lesions had to be larger than 20% of the total hippocampal volume to prolong final escape latencies. The acquisition rate and precision on a probe test without platform were sensitive to even smaller dorsal lesions. The degree of impairment correlated with the lesion volume. In contrast, the lesions of the ventral half of the hippocampus spared both the rate and the precision of learning unless nearly all of the ventral half was removed. There was no significant effect of the location (dorsal or ventral) of damage to the overlying neocortex only. In conclusion, the dorsal half of the hippocampus appears more important for spatial learning than the ventral half. The spatial learning ability seems related to the amount of damaged dorsal hippocampal tissue, with a threshold at about 20% of the total hippocampal volume, under which normal learning can occur.     

Hippocampal modulation of cingulo-thalamic neuronal activity and discriminative avoidance learning in rabbits

Two experiments assessed the effects of 1) combined subicular complex and posterior cingulate cortical lesions on training-induced neuronal activity (TIA) in the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei; 2) hippocampal (Ammon's horn and dentate gyrus) lesions on TIA in cingulate cortex and in the AV and MD thalamic nuclei. The rabbits acquired a conditioned avoidance response (CR), stepping in an activity wheel upon hearing a 0.5-s tone (CS+), in order to prevent a foot-shock scheduled 5 s after tone onset. No response was required after a different, safety-predictive tone (CS-). In experiment 1 the combined subicular and cingulate cortical lesions enhanced thalamic TIA during acquisition and increased CR incidence in the first session of acquisition. These results confirmed the hypothesis that subicular and cingulate cortical efferents are not essential for thalamic TIA or for avoidance learning. Hippocampal lesions (experiment 2) also enhanced thalamic TIA. However, unlike subicular lesions, hippocampal lesions enhanced posterior cingulate cortical TIA as well, especially during extinction training. Hippocampal lesions did not affect CR performance. The results suggested that subicular excitatory efferents are responsible for incrementing cingulate cortical TIA, which is viewed as subserving associative attention. Activity from hippocampus downregulates the cue-elicited neuronal activity of the cingulo-thalamic circuits by suppressing the excitatory influence of the subiculum. The hippocampal influence reduces cingulo-thalamic cue-elicited activation in particular circumstances, such as the onset of CR extinction, when an expected reinforcer is omitted.     

Sparing of function after infant lesions of selected limbic structures in the rat.

The effects, in adult Ss, of limbic lesions produced in infancy were studied in 273 male Wistar rats using weight gain and conditioned emotional response (CER) and condtitioned avodiance response (CAR) acquisition as the critical measures. Ss received bilateral lesions of the amygdala, septum, postventral hippocampus (PH) anterodorsal hippocampus (AH), or frontal cortex either as infants (at 10 days of age) or as adults (at 60 days). Normal and anesthetized control groups were also used. Frontal cortical lesions, AH lesions, and anesthetization had no effect on weights or on CER and CAR acquisition. Both infant and adult amygdala and septal lesions significantly disrupted normal weight gain. Adult-accrued amygdala and PH lesions significantly retarded CER acquisition, and adult septal and PH lesions significantly facilitated CAR acquisition. Infant-accrued amygdala lesions significantly facilitated CAR acquisition, and infant PH lesions had no effect on either task. Results are interpreted to mean that the observed task-specific recovery in early-operated Ss may have been due to some form of functional reorganization. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotransmitters and memory: Role of cholinergic, serotonergic, and noradrenergic systems.

In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study examined the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. A unilateral far-LH lesion decreased feeding and contralateral perifornical LH self-stimulation. 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. Results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)