Neuroscience
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In the symptomatic treatment of mild to moderately severe dementia associated with Alzheimer's disease, donepezil (E2020) has been introduced for the inhibition of acetylcholinesterase activity in the human brain. However, there is no morphological evidence as to how this chemical agent affects the acetylcholinesterase-positive structures in the various areas of the human and the rat CNS. This study demonstrates by histochemical means that donepezil exerts a dose-dependent inhibitory effect in vitro on acetylcholinesterase activity. ⋯ These histochemical results provide the first morphological evidence that, under in vitro circumstances, donepezil is not a general acetylcholinesterase inhibitor in the CNS, but rather selectively affects the different brain areas and, within these, the cholinoceptive and cholinergic structures. The acetylcholinesterase staining in the nerve fibers (innervating the intracerebral blood vessels of the human brain and the extracerebral blood vessels of the rat brain) and at the neuromuscular junction in the diaphragm and gastrocnemius muscle of rat, was also inhibited dose dependently by donepezil. It is concluded that donepezil may be a valuable tool with which to influence both the pre- and the postsynaptic acetylcholinesterase-positive structures in the human and rat central and peripheral nervous systems.
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The influence of embryonic mesencephalic, striatal and mesencephalic/striatal co-grafts on amphetamine- and apomorphine-induced rotation behaviour was assessed in a rat model of multiple system atrophy/striatonigral degeneration type using dopamine D1 ([3H]SCH23390) and D2 ([3H]spiperone) receptor and dopamine re-uptake ([3H]mazindol) autoradiography. Male Wistar rats subjected to a sequential unilateral 6-hydroxydopamine lesion of the medial forebrain bundle followed by a quinolinic acid lesion of the ipsilateral striatum were divided into four treatment groups, receiving either mesencephalic, striatal, mesencephalic/striatal co-grafts or sham grafts. Amphetamine- and apomorphine-induced rotation behaviour was recorded prior to and up to 10 weeks following transplantation. 6-Hydroxydopamine-lesioned animals showed ipsiversive amphetamine-induced and contraversive apomorphine-induced rotation behaviour. ⋯ We propose that the partial reversal of amphetamine-induced rotation asymmetry in double-lesioned rats receiving mesencephalic or mesencephalic/striatal co-grafts reflects non-synaptic graft-derived dopamine release. The changes of apomorphine-induced rotation following transplantation are likely to reflect a complex interaction of graft- and host-derived striatal projection pathways and basal ganglia output nuclei. Further studies in a larger number of animals are required to determine whether morphological parameters and behavioural improvement in the neurotransplantation multiple system atrophy rat model correlate.
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While it has previously been assumed that mesolimbic dopamine neurons carry a reward signal, recent data from single-unit, microdialysis and voltammetry studies suggest that these neurons respond to a large category of salient and arousing events, including appetitive, aversive, high intensity, and novel stimuli. Elevations in dopamine release within mesolimbic, mesocortical and nigrostriatal target sites coincide with arousal, and the increase in dopamine activity within target sites modulates a number of behavioral functions. However, because dopamine neurons respond to a category of salient events that extend beyond that of reward stimuli, dopamine levels are not likely to code for the reward value of encountered events. The paper (i) examines evidence showing that dopamine neurons respond to salient and arousing change in environmental conditions, regardless of the motivational valence of that change, and (ii) asks how this might shape our thinking about the role of dopamine systems in goal-directed behavior.
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We showed recently that conditioned fear to context induces Fos expression in the ventrolateral periaqueductal gray [Neuroscience (1997) 78, 165-177]. Neurons in this region are thought to play an important role in the expression of freezing during conditioned fear. To test the possibility that this activation comes directly from the amygdala, we looked at changes in Fos expression after a unilateral blockade of the ventral amygdalofugal pathway with lidocaine. ⋯ Fos expression remained low on both sides in the non-fear-conditioned animals injected with lidocaine. Finally, although freezing was only partly reduced in the conditioned animals unilaterally injected with lidocaine, it was significantly correlated to the ipsilateral reduction in Fos expression. This study provides direct evidence that the projection from the central nucleus of the amygdala to the ventrolateral periaqueductal gray is activated during fear and that it contributes to the Fos response of the ventrolateral periaqueductal gray.
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For 11 AD cases and four normal elderly controls, post mortem volumes of the hippocampal subdivisions were calculated by using magnetic resonance imaging and histological sections. After at least six weeks of fixation in formalin, brains were examined on a 1.5-T Philips Gyroscan imager producing T1-weighted coronal images with a 3-mm slice thickness. Brains were then processed and embedded in paraffin. ⋯ Strong correlations between the magnetic resonance imaging subvolumes and neuronal counts were found for the hippocampus (r = 0.90, P < 0.001) and the hippocampus/subiculum subvolume (r = 0.84, P < 0.001). We conclude that very accurate volumetric measurements of the whole hippocampal formation can be obtained by using a magnetic resonance imaging protocol. Moreover, the strong correlations between magnetic resonance imaging-based hippocampal volumes and neuronal numbers suggest the anatomical validity of magnetic resonance imaging volume measurements.