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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 289 records · Page 16Linked to original sources
PubMed1978

The effects of dorsal bundle injections of 6-hydroxydopamine on avoidance responding in rats.

1 The effect of injection of 6-hydroxydopamine (6-OHDA) into the fibres of the dorsal noradrenergic bundle on acquisition, retention and extinction of active avoidance in rats were examined. 2 6-OHDA injections severely depleted noradrenaline in all forebrain areas assayed, with the interesting exception of the septum. No significant effect on dopamine concentrations in various forebrain regions was found. 3 Acquisition and retention of active avoidance was not altered by the lesion. Marked resistance to extinction was seen when the unconditioned stimulus (shock) was removed. 4 A comparison with work by other authors in which both forebrain noradrenaline and dopamine were depleted suggest that the alteration in extinction seen in both studies is a noradrenergic effect, whereas the deficits in acquisition and retention found previously are dopaminergic in origin.

Animals↗
PubMed1977

Monoamine involvement in hippocampal self-stimulation.

The roles of noradrenergic and serotonergic projections to the hippocampus were investigated with respect to their involvement in the intracranial self-stimulation of this structure. In the first study, 6-hydroxydopamine-induced lesions of the dorsal tegmental noradrenergic bundle, which depleted hippocampal NE by 97%, had no effect on hippocampal self-stimulation in rats. In the second study, intragastric administration of para-chlorophenylalanine (PCPA) decreased hippocampal self-stimulation, suggesting the importance of a serotonin input in maintaining this behavior. Identical PCPA treatments resulted in temporary depletions of brain serotonin which paralleled the changes in hippocampal self-stimulation. The maximal decreases in both the biochemical and behavioral measures occured at 4 days post-drug. Interpretations of this deficit in hippocampal self-stimulation in terms of gross sensory and/or motor changes were ruled out as animals with lateral hypothalamic electrodes showed increases in self-stimulation paralleling the post-drug serotonin changes. An intra-sessional analysis of the PCPA-induced behavioral changes revealed that lateral hypothalamic self-stimulation was facilitated mainly during the first hour of the two-hour test sessions, whereas the depression in hippocampal self-stimulation occurred primarily in the last hour of the sessions. The differential effects of PCPA on lateral hypothalamic and hippocampal self-stimulation provide evidence against simple monoamine theories of reinforcement.

Animals↗
PubMed1977

On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine.

The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.

Animals↗
PubMed1977

Evidence for interactions between central noradrenergic neurons and adrenal hormones in learning and memory.

The role of ascending noradrenergic projections in the acquisition and retention of a passive avoidance step-down response was evaluated by means of bilateral stereotaxic 6-hydroxydopamine-induced lesions of these systems. Lesions of the dorsal NA bundle alone, or in combination with lesions of the ventral NA bundle, failed to influence either the acquisition or retention of the passive avoidance response. In contrast, animals subjected to dorsal and ventral NA bundle lesions and adrenalectomy exhibited severe deficits in both the acquisition and retention of this response, and this effect was of the same magnitude as was observed after posttrial injections of diethyldithiocarbamate (DDC, 300 mg/kg). Adrenalectomy by itself had a small but significant effect on retention but did not influence acquisition of the response. The results are discussed with reference to the possibility that interactions between adrenal hormones and central NA mechanisms may serve important roles in learning and memory. However, the data provide no support for the hypothesis that central NA neurons are, by themselves, critically involved in these phenomena.

Adrenalectomy↗
PubMed1977

Schedule dependent changes in operant responding after lesions of the dorsal tegmental noradrenergic projection.

The present experiments examined the role of the dorsal tegmental noradrenergic bundle (DTNB) in operant responding for food under various schedules of reinforcement. This catecholaminergic neuronal system originates in the nucleus locus coeruleus and has diffuse projections to hippocampus and cerebral cortex. Bilateral stereotaxic injections of 6-hydroxydopamine into the DTNB of rats reduced hippocampal-cortical noradrenaline to less than 5% of control levels. Animals with these lesions acquired a continuously reinforced (CRF) bar-press response at the same rate as controls. Compared to controls rats with DTNB lesions responded at significantly lower rates on a variable interval 30 (VI 30) schedule. Extinction after VI 30 responding did not differ significantly between control and lesioned animals. In another experiment no significant difference was observed between DTNB lesioned and control groups on the rate of responding on a fixed ratio 30 (FR 30) schedule. The results are discussed with reference to previous reports indicating changes in operant responding after intraventricular injections of 6-hydroxydopamine. The data failed to support the hypothesis that the DTNB is critically involved in learning and memory.

Animals↗
PubMed1976

Retrograde amnesia after electrical stimulation of the substantia nigra: mediation by the dopaminergic nigroneostriatal bundle.

Stimulation of the zona compacta of the substantia nigra (SNC) has been reported to impair the long-term retention of a passive avoidance step-down task. In the present experiments it was observed that previous ipsilateral lesions of the dopaminergic nigro-neostriatal bundle (NSB) with 6-hydroxydopamine blocked the stimulation-induced memory deficit. Unilateral or bilateral lesions of the dopaminergic NSB did not by themselves disrupt acquisition or retention of the passive avoidance task. In addition, the memory deficit observed after electrical stimulation of the caudate-putamen was not reduced by ipsilateral NSB lesions. These results indicate that the retention deficit produced by stimulation of the SNC was mediated by the dopaminergic NSB. However, in view of the fact that lesions of this projection did not affect acquisition or retention of the step-down task, it is suggested that this system is not critically involved in learning and memory. Rather, it is hypothesized that stimulation of the SNC results in an excess release of dopamine in the caudateputamen which interferes with neurochemical and neurophysiological events in this structure which are important substrates for long-term memory.

Amnesia↗
PubMed1976

Differential effects of para-chlorophenylalanine on self-stimulation in caudate-putamen and lateral hypothalamus.

Rats were prepared with chronic bipolar electrodes aimed at either the caudate-putamen or lateral hypothalamus and those displaying consistent self-stimulation were given additional training at half-maximal current intensities. All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established. Responding in both brain areas was suppressed 24 h after drug treatment. The next day, self-stimulation rates in the hypothalamus increased to 115% of pre-drug levels reaching a level of 180% by the third day of post-drug testing. In contrast, self-stimulation of sites in the neostriatum continued to decline, with minimal levels reaching 48% of control on the fourth post-drug day. Self-stimulation rates in both groups had returned to control levels by post-drug day 6. These data indicate that the role of serotonergic mechanisms in brain stimulation is locus specific, and that the specific nature of this role may be determined by interaction with other neurochemical systems. The possible interaction between dopaminergic and serotinergic mechanisms in the neostriatum is discussed as a model of self-stimulation in this region of the brain.

Animals↗
PubMed1976

Evidence that self-stimulation of the region of the locus coeruleus in rats does not depend upon noradrenergic projections to telencephalon.

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.

Animals↗
PubMed1976

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward.

Rats were implanted with electrodes in the lateral hypothalamus, put on a 22-h food deprivation schedule and trained to bar-press for ICS and for food on a CRF schedule. Haloperidol (0.08 mg/kg) and pimozide (0.22 mg/kg) significantly decreased responding for both reinforces, although responding for ICS was decreased more than it was for food. The same doses of these drugs did not decrease food consumption of a 15-min ad libitum test after 22-h of food deprivation, suggesting that the decreased bar-pressing for food was not the result of anorexia or reduced motivation for food. When similar rates of responding for ICS and for food were obtained on a V1 60 schedule, haloperidol (0.1 mg/kg) reduced responding for food and ICS to a similar extent. Thus, when baseline rate is controlled for, neuroleptics do not selectively reduce responding for ICS. In addition, examination of cumulative response records revealed that rather than producing an extinction curve, as would be predicted if neuroleptics reduced the rewarding properties of ICS, haloperidol produced a uniform decrease in the rate of responding throughout the experimental session. Similar results were obtained with intraventricular 6-hydroxydopamine (6-OHDA) injections. While these experiments do not exclude the possibility that dopaminergic (DA) systems participate in some central reinforcement mechanisms, they suggest that neuroleptics and 6-OHDA decrease responding for food or ICS primarily by impairing the function of DA systems critically involved in the initiation or maintenance of operant behaviour rather than by interfering with reward.

Animals↗
PubMed1976

Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen.

An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions.

Animals↗
PubMed1976

Abolition of nomifensine-induced stereotypy after 6-hydroxydopamine lesions of ascending dopaminergic projections.

The effects of bilateral focal injections of 6-hydroxydopamine into the zona compacta of the substantia nigra (SNC) on nomifensine-induced stereotypy were examined in the rat. These lesions reduced neostriatal dopamine levels to less than 1 percent of control levels. They also abolished nomifensine-induced stereotyped behavior. It is suggested that nomifensine-induced stereotypy is mediated via a presynaptic action on dopamine uptake and release.

Animals↗