Paavo Riekkinen

Similar memory impairments found in medial septal-vertical diagonal band of Broca and nucleus basalis lesioned rats: Are memory defects induced by nucleus basalis lesions related to the degree of non-specific subcortical cell loss?

The function of nucleus basalis (NB) and medial septal-vertical diagonal band of Broca (MS-VDBB) in a place navigation task requiring reference memory was investigated. Two subclasses of nucleus basalis ibotenic acid-lesioned rats could be identified: a group having both extensive non-specific subcortical damage and severely impaired learning behavior, and a less impaired group with correspondingly less subcortical damage. The depletion of cortical cholinergic enzymes was slightly higher in the group of NB-lesioned rats with extensive subcortical lesions than in the group with smaller lesioned areas. In the hippocampus of both of these NB-lesioned groups, cholinergic innervation remained unchanged. Ibotenic acid lesioning restricted to the MS-VDBB depleted hippocampal cholinergic innervation, but not the innervation of the frontal cortex, and also led to impaired learning behavior. Of all the lesioned rats, the most impaired were the NB-lesioned rats with large non-specific subcortical lesion.

Relationship between the cortical choline acetyltransferase content and EEG delta-power

Destruction of the nucleus basalis abolished normal spectral power only in the frontal cortex, where choline acetyltransferase (ChAT) activity was lower. In lesioned animals, delta-power was increased and alpha-power decreased. The increase in delta-power during immobility correlated with a reduction in ChAT activity. High-voltage spindles occurred more frequently after cholinergic denervation. The results suggest that spectral power and high-voltage spindle analysis might serve as a useful tool for evaluating the efficacy of pharmacological strategies aimed at alleviating the cholinergic deficit.

Effects of quisqualic acid nucleus basalis lesioning on cortical EEG, passive avoidance and water maze performance.

The study examines the effects of unilateral quisqualic acid nucleus basalis (NB) lesioning on cortical EEG and learning behavior. Lesions produced both gliosis in the ventral pallidum and a marked reduction in the cortical ChAT activity. Normal cortical EEG activity was abolished on the side of NB lesion, i.e., slow wave activity and the incidence of high voltage spindles was higher on the side of lesion compared with the control side. NB lesioning impaired passive avoidance retention, but not spatial learning ability. These results suggest that EEG and passive avoidance deficits induced by NB quisqualic acid lesion may result from the damage specifically to cholinergic neurons. Thus, the restoration of EEG and passive avoidance performance defects in quisqualic-lesioned rats may be used as an index of the efficacy of the cholinergic replacement therapies.

The effects of THA on medial septal lesion-induced memory defects

Electrolytic lesioning of the medial septum (MS) was used to assess the effectiveness of tacrine (THA) in reversing lesion-induced spatial memory deficits in a water-maze. Lesioned animals were injected with either 3 mg/kg or 5 mg/kg of THA intraperitoneally 15 min prior to daily behavioral training. One group of the lesioned and sham-operated animals received saline. All animals underwent two training trials each day for a period of ten days, after which a spatial probe trial was performed and assessed. The accurate placement of MS lesions resulted in lowered acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity within the hippocampus of lesioned rats. Lesioning of the MS also impaired the learning performance in locating the escape platform during training and decreased the spatial bias during the probe trial. A lower dose of THA (3 mg/kg) significantly reversed the path length increase and spatial bias decrease induced by MS lesioning, but had no effect on escape latency. However, comparison between the saline- and THA- (5 mg/kg) injected MS-lesioned rats showed no significant differences in either escape latency or spatial bias. The present results support the use of cholinesterase inhibitors in further treatment trials of geriatric memory disorders.

The effects of concurrent manipulations of cholinergic and noradrenergic systems on neocortical EEG and spatial learning

In the spatial learning test, young animals were divided into three groups receiving saline, scopolamine (0.15 mg/kg), or scopolamine (0.8 mg/kg). Half of the animals in each group were lesioned with DSP-4 to destroy noradrenergic fibers. DSP-4 lesions did not produce any significant impairment alone or in combination with a lower dose of scopolamine (0.15 mg/kg), but they did further augment the scopolamine (0.8 mg/kg)-induced defect. In the electroencephalography (EEG) experiment, both control rats and DSP-4-lesioned rats were recorded after receiving saline, scopolamine (0.15 mg/kg), and scopolamine (0.8 mg/kg) injections. Scopolamine induced a dose- and behavioral state-dependent EEG slowing, whereas DSP-4 lesions did not change either baseline EEG activity or EEG reactivity to scopolamine.

Interaction between raphe dorsalis and nucleus basalis magnocellularis in the regulation of high-voltage spindle activity in rat neocortex

In the present study we compared the effects of an ibotenic acid lesion of the nucleus basalis magnocellularis (NBM), a 5,7-dihydroxytryptamine lesion of the raphe dorsalis (RD) and a combined RD and NBM lesion on the regulation of neocortical electrical activity in freely moving rat. NBM lesions (choline acetyltransferase decrease: frontal cortex 29%, occipital cortex 23%) increased both slow wave amplitudes and waking immobility-related high-voltage spindles (HVS). Although RD lesions (serotonin decrease: frontal cortex 67%, occipital cortex 68%) alone did not affect neocortical electrical activity, the lesion aggravated the increase of HVSs induced by an NBM lesion. The present results demonstrate an interaction between the RD and NBM in regulating cortical functions.

Dose- and parameter-dependent effects of atipamezole, an α2-antagonist, on the performance of rats in a five-choice serial reaction time task

The present study investigated whether atipamezole (ATI), a potent alpha 2-adrenoceptor antagonist that increases the release of noradrenaline in brain, improves attention in rats. Thus, the effects of ATI on the performance of adult male rats in the five-choice serial reaction time task were studied. Food-deprived rats were trained to detect and respond to brief flashes of light presented randomly in one of five spatially diverse locations. The effects of single-dose administration of ATI (0.03-3.0 mg/kg) on the performance of rats under different parametric manipulations of the task were tested: 1) the visual stimuli were presented at unpredictable intertrial intervals (ITIs) or b) the intensity (brightness) of visual stimuli was reduced, thus placing an additional load on attentional processing for animals. Presenting the stimuli earlier than normally or reducing its intensity markedly impaired the choice accuracy of rats. At doses of 0.03, 0.3, and 1.0 mg/kg, ATI improved the choice accuracy of rats when tested using reduced stimulus intensity. ATI 3.0 mg/kg did not affect accuracy performance when tested using reduced stimulus intensity but impaired it when tested using unpredictable ITIs. The other doses of ATI (0.03, 0.3, and 1.0 mg/kg) did not markedly affect choice accuracy of rats tested using unpredictable ITI. Our results could be explained by the assumption that an acute, systemic administration of ATI affects arousal mechanisms and facilitates the processing of visual stimuli related to reward.

EEG and CT findings in patients with panic disorder

Fifty-four patients with panic disorder were investigated using extensive electroencephalographic (EEG) recordings and computerized tomography (CT). Fifteen (28%) of these patients had previously been treated for temporal lobe epilepsy or were considered to have another neurological disorder. EEG recordings showed increased slow-wave activity in 13 (24%) patients and CT scan revealed incidental abnormalities in 6 (20%) of the 30 patients investigated. Taking into account the limitations of the methods applied, the present results indicate that clear-cut epileptic EEG patterns only rarely occur in panic disorder: the vast majority of panic patients exhibit normal EEG and CT findings.

The effects of guanfacine, α-2 agonist, on the performance of young and aged rats in spatial navigation task

The aim of the present experiment was to study the effects of a low dose (0.001 mg/kg) of guanfacine, alpha-2 agonist, on the acquisition and retention of a water maze task measuring spatial reference memory in young and aged rats. Aged rats were impaired in the acquisition of this task. Both young and aged rats treated with guanfacine had shorter escape latencies than their saline treated counterparts. However, guanfacine treatment increased the speed of swimming in aged rats. According to the results of the probe trial, guanfacine may slightly improve the acquisition/retention of water maze task in young rats, whereas it may slightly impair the acquisition/retention of aged rats. The results suggest that a low dose of guanfacine administered peripherally may have different effects on young and aged rats in water maze performance, and a low dose of guanfacine does not improve spatial reference memory in aged rats.

Effect of alpha2 antagonists and an agonist on EEG slowing induced by scopolamine and lesion of the nucleus basalis

In the present study, the effects of an alpha 2 agonist (clonidine, 1.0 mg/kg i.p.) and two antagonists (atipamezole, 1 and 10 mg/kg s.c. and yohimbine, 3.0 mg/kg i.p.) were studied on the EEG activity of naive rats, pretreated with either saline or scopolamine (0.8 mg/kg), or rats receiving lesioning of the nucleus basalis. The alpha 2 antagonists increased fast activity (alpha and beta). Clonidine increased slow wave activity (increased in spectral amplitudes) during periods of immobility and mobility. The EEG slowing, induced by scopolamine, was not alleviated by antipamezole or yohimbine, but in immobile rats, an increase in the delta and theta amplitudes was augmented by clonidine. In nucleus basalis-lesioned rats, the increase in delta activity was partially normalised by the alpha 2 antagonists. The decrease in the beta amplitude, induced by lesioning of the nucleus basalis, was not alleviated with either atipamezole or yohimbine. Clonidine increased the slow wave activity in nucleus basalis-lesioned rats and induced an increase in delta and theta bands during immobility. No changes were induced by clonidine in the EEG recorded from rats with lesions of the nucleus basalis.