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  • 1
    Electronic Resource
    Electronic Resource
    Behavioral asymmetries and neurochemical changes after unilateral lesions of tuberomammillary nucleus or substantia nigra (1998)
    Springer
    Experimental brain research 120 (1998), S. 273-282 
    Details
    ISSN: 1432-1106
    Keywords: Key words Basal ganglia ; Hippocampus ; Tectum ; Dopamine ; Serotonin ; Histamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the rat have shown that the hypothalamic tuberomammillary nucleus, the major source of neuronal histamine, is related to mechanisms of learning, memory, reinforcement, and functional recovery. These functional relationships were found to be partly lateralized. Therefore, we decided to analyze whether unilateral ibotenic acid lesions aimed at this brain region would acutely lead to asymmetries in open-field behavior, and whether they would affect the biogenic amines dopamine and serotonin in the neostriatum, hippocampus, and tectum. We compared this manipulation with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta and with unilateral ibotenic acid lesions of the substantia nigra pars reticulata. These lesions were investigated because all three brain areas are anatomically linked to the neostriatum, are related to the neurotransmitters dopamine and serotonin, and play a role in behavioral asymmetry and functional recovery. In support of previous findings, our data show that 6-hydroxydopamine lesions of the substantia nigra pars compacta led to an ipsiversive asymmetry in turning and scanning. Ibotenic acid lesions of the adjacent pars reticulata led to contraversive turning, whereas thigmotactic scanning was reduced bilaterally. In contrast, ibotenic acid lesions of the tuberomammillary nucleus did not affect turning, but led to an ipsilateral asymmetry in scanning. Neurochemically, the 6-hydroxydopamine lesion was mainly characterized by the well-known ipsilateral neostriatal dopamine depletion and increased residual dopamine activity. In hippocampus and tectum, these transmitters were not specifically affected, except for an asymmetry of serotonin in the superior colliculus. The ibotenic acid lesions of the pars reticulata did not deplete neostriatal dopamine, indicating that they spared the dopaminergic output of the substantia nigra. In contrast, they affected dopaminergic and serotonergic measures in the colliculi, which may be due to damage of the nigral GABAergic projection to this brain area. In animals with unilateral ibotenic acid lesions of the tuberomammillary nucleus, several markers of dopaminergic and serotonergic acitivity were increased in the neostriatum, tectum, and hippocampus. This effect may have been due to the loss of inhibition otherwise provided by the wide-ranging histaminergic output of the tuberomammillary nucleus. These results are discussed with respect to the major outputs of the three brain areas, their potential impacts on neurotransmitters in their projection sites, and their role in behavioral asymmetry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050401
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  • 2
    Electronic Resource
    Electronic Resource
    Intranasal Administration of the Dopaminergic Agonists l-DOPA, Amphetamine, and Cocaine Increases Dopamine Activity in the Neostriatum: A Microdialysis Study in the Rat (1997)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 68 (1997), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug l-DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of l-DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal l-DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that l-DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1997.68010233.x
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  • 3
    Electronic Resource
    Electronic Resource
    Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity (1993)
    Springer
    Psychopharmacology 112 (1993), S. 147-162 
    Details
    ISSN: 1432-2072
    Keywords: Peptides ; Tachykinins ; Substance P fragments ; Inhibitory avoidance learning ; Conditioned place preference ; Nucleus basalis magnocellularis ; Dopamine ; Neostriatum ; Nucleus accumbens ; In vivo microdialysis ; Neurodegeneration ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinforcement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244906
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  • 4
    Electronic Resource
    Electronic Resource
    Stimulation of D1- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions (1995)
    Springer
    Psychopharmacology 119 (1995), S. 145-154 
    Details
    ISSN: 1432-2072
    Keywords: Turning ; Thigmotactic scanning ; Locomotion ; Grooming ; 6-Hydroxydopamine ; Neostriatum ; Substantia nigra ; Dopamine ; Dopamine receptors ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We had previously found that in animals with moderate nigro-striatal dopamine (DA) lesions (i.e. 45–65% residual neostriatal DA) the mixed D1/D2-agonist apomorphine induced ipsiversive rather than the usual contraversive turning found after more radical DA lesions. Since this result promised to provide a behavioral animal model for pre-clinical Parkinson's disease, we hoped to delineate the responsible receptor by challenging with selective D1- and D2-agonists. Thus, in the present study, the behavioral effects of the D1-agonist SKF38393 (5.0 mg/kg) and the D2-agonist LY171555 (0.5 mg/kg) were tested in drug-naive rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal DA system. This analysis was performed dependent on the degree of the lesion, classified post-mortem with respect to the level of residual DA in the neostriatum: 〈20%, 20–45%, 45–65%, and 〉65% (as percentage of the intact hemisphere). The measures of turning, thigmotactic scanning and locomotion did not yield differences between animals treated with the D1-agonist and vehicle-treated rats. For example, animals with severe lesions (residual DA 〈20%) showed ipsiversive asymmetries in turning and scanning, which were similar after vehicle or the D1-agonist, both with respect to degree and time-course. However, the analysis of grooming behavior, which was performed in a subset of animals with moderate lesions yielded differences between vehicle and the D1-agonist, since the duration of grooming was increased after SKF38393. In contrast to the D1-agonist, behavioral effects after the D2-agonist LY17155 were evident in all behavioral measures. The general response to this agonist could be characterized by a rapid decrease of behavioral activity including turning, scanning, locomotion and grooming. Although we failed to find significant behavioral asymmetries with either agonist, a micro-analysis showed evidence for selective effects after the D2-agonist, since a contraversive asymmetry in turning (and scanning) became apparent between 45 and 60 min after injection in animals with severe lesions (residual DA of about 10% or less), and since there was a weak ipsiversive turning asymmetry in animals with residual DA levels of 45–65%. Such asymmetries were not observed after vehicle or the D1-agonist. The possible physiological mechanisms of these effects, i.e. DA receptor mechanisms and DA availability, are discussed in the context of results from previous experiments using lesioned or intact animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246155
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  • 5
    Electronic Resource
    Electronic Resource
    Different effects of scopolamine on extracellular acetylcholine levels in neostriatum and nucleus accumbens measured in vivo: possible interaction with aversive stimulation (1994)
    Springer
    Journal of neural transmission 97 (1994), S. 13-25 
    Details
    ISSN: 1435-1463
    Keywords: Acetylcholine receptor antagonist ; striatum ; rat ; microdialysis ; reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thein vivomicrodialysis technique was used to measure extracellular concentrations of acetylcholine (ACh) in the neostriatum (NS) and nucleus accumbens (NAc) of freely moving rats after intraperitoneal administration of the muscarinic receptor antagonist scopolamine (0.5mg/kg) or vehicle. Simultaneously, behavior was monitored. The administration of scopolamine induced an increase in extracellular ACh levels in the NS, which reached a maximum of about 185% within one hour after injection and returned to baseline values about three hours after injection. In the NAc, an increase of similar time-course was observed; however, this increase reached a maximum of 250%, which was significantly higher than the one observed in NS. These changes in ACh levels were accompanied by enhanced locomotion, rearing and grooming; however, the behavioral changes were of shorter time-course than those of extracellular ACh. The injection of vehicle did not affect ACh levels in NS, but induced a significant increase (60%) in the NAc. The levels of behavioral activity after vehicle injection did not differ from pre-injection levels. These results suggest, that the cholinergic systems in the NAc and NS are differently affected by peripheral administration of both scopolamine and vehicle. The differential effects of scopolamine in NS and NAc could reflect pharmacodynamic differences between these two striatal brain areas, perhaps due to a higher density of cholinergic interneurons or muscarinic autoreceptors in the NAc in comparsion to the NS. However, the increase of extracellular ACh observed after vehicle injection suggests that factors such as aversive stimulation through the injection procedure can increase ACh release in the NAc and that such a mechanism can interact within the action of scopolamine. Thus, the stronger action of scopolamine on extracellular ACh in the NAc might be an additive effect of the drug with that of the injection procedure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01277959
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