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Biomedical subjects

S D Iversen

Publications and source records attributed to S D Iversen.

At least 145 records · Page 8Linked to original sources
PubMed1982

Sensorimotor impairments following localized kainic acid and 6-hydroxydopamine lesions of the neostriatum.

Rats received either control saline, 6-hydroxydopamine (6-OHDA) or kainic acid (KA) unilateral lesions of 5 different foci in the neostriatum. Both KA and 6-OHDA lesions in the mid-ventral focus resulted in a substantial and prolonged impairment in sensorimotor orientation to contralateral stimuli. At all other placements 6-OHDA induced a temporary mild impairment, and KA had no detectable biasing effects. The results suggest that the neostriatum is topographically heterogeneous in the mediation of this particular aspect of sensorimotor performance.

Animals↗
PubMed1982

The behavioural effects of a novel substance P analogue following infusion into the ventral tegmental area or substantia nigra of rat brain.

The behavioural response following infusion of a novel, stable substance P (SP) analogue, DiMe-C7, into the ventral tegmental area (VTA) of rats was characterized and contrasted with the response to an equal dose of the parent compound SP. DiMe-C7 produced a longer-lasting behavioural stimulation than SP as evidenced in several behaviours, including locomotor activity, wet dog shakes, rearing and grooming. DiMe-C7-induced locomotor activity and rearing were potentiated by concurrent peripheral administration of D-amphetamine and blocked by pretreatment with haloperidol. Such responses to DiMe-C7 may thus be dependent upon dopaminergic activity. When given immediately following VTA infusion of DiMe-C7, morphine decreased, while naloxone had no effect upon most behavioural measures. The effect of methysergide on DiMe-C7 or SP into the substantia nigra reticulata produced a pattern of responses similar to nature to those produced by VTA infusion but different with respect to time course. These findings suggest that DiMe-C7 is a metabolically stable analogue of substance P which manifests prolonged actions on behaviour when centrally administered. Further, a role for central dopaminergic mechanisms is implicated in DiMe-C7-induced behavioural action.

Animals↗
PubMed1982

Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions.

A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.

Animals↗
PubMed1982

Behavioural effects of substance P through dopaminergic pathways in the brain.

Some of the highest concentrations of substance P in forebrain are found in areas where dopaminergic neurons arise or terminate. In the rat, native substance P has been injected directly into brain areas where interactions between substance P and dopamine are suspected. In the ventral tegmental area (A10 dopamine neurons), bilateral infusions of substance P induce locomotor activity and exploration. It is concluded that substance P activates A10 dopamine neurons innervating the limbic system because (i) the behavioural effects resemble those seen after systemic treatment with low doses of d-amphetamine, a drug response known to depend on the integrity of the A10 dopamine neurons; (ii) lesions to the A10 dopamine neurons abolish the behavioural response to intracerebrally infused substance P; and (iii) dopamine antagonist drugs abolish the response to substance P. In parallel experiments substance P was injected into the origins of the nigrostriatal (A9 dopamine neurons) system and found to produce stereotyped behaviour. Substance P analogues protected from enzymic degradation have been studied in these model systems. The prolongation of the behavioural effects is correlated with the presence of undegraded substance P in the ventral tegmental area. Unrelated behavioural responses are also observed, which appear not to be mediated by dopamine neurons, and probably reflect the spread of stable substance P from the ventral tegmental area to other brain sites.

Animals↗
PubMed1982

Spontaneous and drug-induced rotation following localized 6-hydroxydopamine and kainic acid-induced lesions of the neostriatum.

Twelve groups of rats received small localized lesions produced by either 6-hydroxydopamine (6-OHDA) or kainic acid (KA) in one of six placements in the right neostriatum. All groups lesioned with 6-OHDA showed ipsilateral spontaneous and amphetamine-induced rotation and contralateral apomorphine-induced rotation. All groups lesioned with kainic acid showed ipsilateral spontaneous rotation on day 1 following the lesion but contralateral rotation by day 8, and no significant rotation to injections of either amphetamine or apomorphine. The histology suggested that the lesions were topographically specific, and it is therefore concluded that the neostriatum is topographically homogeneous in the mediation of rotational behaviour as measured in automated rotometers.

Animals↗
PubMed1982

Neurotoxic lesions of ventrolateral but not anteromedial neostriatum in rats impair differential reinforcement of low rates (DRL) performance.

In two separate experiments, rats received either kainic acid (KA), 6-hydroxydopamine (6-OHDA) or control lesions bilaterally into either the anteromedial or ventrolateral neostriatum. Both ventrolateral neurotoxic lesions disrupted post-operative body weight regulation and the acquisition of a DRL-20 sec operant schedule of reinforcement. The pattern of operant responding suggested that these animals had an impairment in response sequencing or switching. Rats with anteromedial lesions manifested neither body-weight nor DRL impairments.

Afferent Pathways↗
PubMed1982

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Afferent Pathways↗
PubMed1981

Behavioural recovery following transplantation of substantia nigra in rats subjected to 6-OHDA lesions of the nigrostriatal pathway. II. Bilateral lesions.

Rats with a unilateral transplant of embryonic substantia nigra, placed in a cortical cavity overlying the caudate-putamen, were compared with control animals on a range of behavioral tests following bilateral 6-OHDA lesions of the ascending dopaminergic nigrostriatal pathway. Tests designed to reveal behavioural asymmetry--such as spontaneous, tail-pinch and amphetamine-induced rotation, sensorimotor orientation, and side preference in a T-maze--revealed that the rats with bilateral 6-OHDA lesions and a unilateral transplant are similar to unilaterally lesioned animals with one intact nigrostriatal pathway. Both transplanted and bilaterally lesioned control rats became spontaneously akinetic after the second 6-OHDA lesion. This akinesia could be reversed by a low dose of amphetamine (0.5 mg/kg) in the transplanted but not in the non-transplanted control rats. The attenuated effects of apomorphine and L-DOPA on activity and rotation suggest that the nigral transplant produced a partial reversal of receptor supersensitivity following the 6-OHDA lesion on the same side as the transplant. However, other effects of the bilateral 6-OHDA lesion, including the development of aphagia, adipsia and akinesia, were not reversed by the presence of the transplant. The transplants were shown by fluorescence histochemistry to have densely reinnervated the dorsal parts of the denervated caudateputamen on the side ipsilateral to the transplant. The results show that intracortical nigral grafts reinnervating parts of the dorsal caudate-putamen can reverse some, but not all, functional impairments associated with bilateral destruction of the nigrostriatal pathway.

Animals↗
PubMed1981

Grafts of embryonic substantia nigra reinnervating the ventrolateral striatum ameliorate sensorimotor impairments and akinesia in rats with 6-OHDA lesions of the nigrostriatal pathway.

Previous studies have shown that transplants of embryonic substantia nigra, which reinnervate the dorsal neostriatum, can compensate for certain, but not all, behavioural deficits induced by unilateral or bilateral destruction of the nigrostriatal dopamine pathways in adult rats. The present study shows the nigral transplants which are placed in the lateral cortex so as to reinnervate ventral and lateral parts of the neostriatum, give an entirely different pattern of behavioural recovery. Thus, the laterally placed grafts were more efficient than the previous dorsally placed ones in compensating for the sensorimotor asymmetry in unilaterally lesioned animals, and the akinesia seen after bilateral lesions. Conversely, the drug-induced motor asymmetry which was completely abolished by the dorsal grafts was not significantly affected in the present animals. These results support the idea of topographic heterogeneity with respect to striatal functions, and suggest that the technique can be used as a tool for more detailed analysis of the functional organization of the meso-telencephalic dopamine systems and the functional heterogeneity of the dopaminergically innervated striatal-based forebrain regions.

Animals↗
PubMed1981

The behavioural effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus.

Two stable analogues of enkephalin D-Ala2-Met5-enkephalinamide (DAMA) and D-Ala2,D-Leu5-enkephalin (DADLE) injected bilaterally into the ventral tegmental area (VTA) induced locomotion, characterized by bursts of morphine-like activity. The response of DADLE was blocked by systemic-alpha-flupenthixol (0.2 mg/kg) and naloxone (1 mg/kg). At higher doses of enkephalins in the VTA, stereotypy behaviour involving gnawing, became apparent. When injected bilaterally into the globus pallidus (GP), both analogues induced a dose-dependent increase in locomotor activity but stereotypy was not observed. The locomotor behaviour induced by DADLE was blocked by naloxone but not by alpha-flupenthixol. These results suggest that naloxone-sensitive opiate receptors modulate, at a number of different sites, the neural pathways involved in the expression of behavioural activity.

Animals↗
PubMed1981

Behavioural recovery following transplantation of substantia nigra in rats subjected to 6-OHDA lesions of the nigrostriatal pathway. I. Unilateral lesions.

The ability of embryonic substantia nigra transplants to compensate for behavioural deficits induced by unilateral destruction of the nigrostriatal dopamine pathway has been investigated in adult rats. Six days following unilateral 6-OHDA lesions of the nigrostriatal pathway, the adequacy of the lesion was assessed by measurement of the intensity of ipsilateral amphetamine-induced rotation. All rats then received surgical cavities in the cortex overlying the head of the caudate-putamen on the lesioned side. In 51 rats, transplants of embryonic substantia nigra were placed on the dorsal surface of the caudate-putamen, and the remaining 19 rats served as unilateral lesioned controls. Behavioural testing was conducted approximately 3 months after transplantation: (a) the transplant animals alone showed a marked reduction in ipsilateral rotation induced by 5 mg/kg amphetamine ('compensation'); (b) although both transplanted and control rats expressed equal contralateral rotation at a dose of 0.25 mg/kg apomorphine, the transplant animals alone showed a marked reduction in rotation at a lower dose of 0.05 mg/kg; (c) the transplanted rats showed less asymmetry in spontaneous rotational behaviour than controls, and the asymmetry was further reduced by mild tailpinch; (d) when tested for spontaneous choice behaviour in a T-maze, control rats showed 97% selection of the arm ipsilateral to the 6-OHDA lesion, whereas the transplanted rats that were well compensated on the amphetamine rotation test turned to the contralateral side on 30-40% of choices; (e) no transplant-induced changes were found in contralateral sensory inattention on a sensorimotor test battery, whether tested spontaneously or under mild tailpinch-induced activation. The results support the conclusion that dopaminergic reinnervation of the dorsal neostriatum is capable of inducing functional recovery in many, but not all, behavioural tests which involve side choice or bias, not only after pharmacological activation but also in the spontaneously behaving animal.

Amphetamine↗
PubMed1981

Functional reactivation of the deafferented neostriatum by nigral transplants.

Functional deficits following brain lesions can be due not only to the disruption of conduction in specific input and output pathways passing through the site of injury, but also to the loss of important regulatory systems controlling the functional state of neuronal circuitries in areas distant from the lesion. For example, the behavioural disturbances that result from lesions of the nigrostriatal dopamine (DA) pathways can be reversed by administration of dopamine receptor-activating drugs, such as L-dopa or apomorphine. This suggests that the lesioned dopaminergic system, rather than conveying specific input and output signals, is normally acting on neuronal machineries whose activity levels are set by the activity at the dopaminergic synapses. Thus the neurological deficits resulting from these lesions are due to functional inactivation of otherwise intact neostriatal circuitries. Previous studies have shown that intracerebral transplants of embryonic substantia nigra can compensate for drug-induced as well as spontaneous asymmetric motor behaviour (expressed as a tendency to move in circles towards the lesioned side), whereas the sensorimotor asymmetry, which is pronounced in rats with a unilateral lesion of the nigrostriatal DA pathway, was unaffected by the transplant. We report here that restoration of striatal dopaminergic neurotransmission by nigral transplants in animals with bilateral, complete lesions of the nigral transplants in animals with bilateral, complete lesions of the nigrostriatal DA pathways can reinstate not only certain aspects of spontaneous motor behavior, but also sensorimotor orientation and sensory attention on the side of the body contralateral to the graft.

Animals↗