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Anxiogenic behavior in the light-dark paradigm follwoing intraventricular administration of cholecystokinin-8S, restraint stress, or uncontrollable footshock in the CD-1 mouse.

The influence of restraint stress (0, 15, 30, or 60 min), uncontrollable footshock (0, 15, 30, or 60 shocks), or intraventricular CCK-8S administration (0, 5, 25, or 50 ng delivered in a 1 microliter volume) were evaluated on transition frequency and cumulative time in light among CD-1 mice in the light-dark paradigm. Mice exposed to restraint stress of either 15 or 60 min were indistinguishable from nonrestrained animals, while the 30-min session of restraint decreased time in light and transition scores. The presentation of 15, 30, or 60 uncontrollable footshocks were equally effective in decreasing cumulative time in light but had no effect on transition scores. Intraventricular infusion of 25 and 50 ng doses of cholecystokinin-8S reduced cumulative time in light and transition frequency in CD-1 mice relative to vehicle or 5 ng CCK-8S-treated animals in the light-dark paradigm. The time in light and transition data secured among mice with repeated light-dark exposure and 30 min of restraint were comparable to the corresponding scores secured when performance was only evaluated on trial 1. Transition scores were reduced on trial 1 of mice exposed to 30 min of footshock, but time in light was reminiscent of the performance detected among mice with prior light-dark experience. Potential neurochemical correlates associated with the anxiogenic effects associated with stressor exposure and CCK-8S administration in the light-dark task are discussed.

Animals↗

Evidence that behavioural and electrocortical sleep induced by guanfacine is due to stimulation of alpha 2-adrenoceptors.

The effects of guanfacine and other drugs acting at alpha 1- and alpha 2-adrenoceptors on behaviour, electrocortical activity and ECoG spectrum power were studied in chicks and rats. Guanfacine, given systematically in chicks, produced behavioural and electrocortical slow-wave sleep lasting 100-200 min, depending on the dose; these effects were prevented by yohimbine, a selective antagonist, at alpha 2-adrenoceptors and potentiated by prazosin, a selective antagonist, at alpha 1-adrenoceptors. Similar behavioural and electrocortical effects were obtained after systemic or intraventricular infusion of guanfacine in rats. In addition, a significant increase in total and in lower frequency band (0-4; 4-8 Hz) voltage power was observed. Behavioural and ECoG effects of guanfacine were prevented by phentolamine or yohimbine, whereas prazosin and propranolol were ineffective. Yohimbine itself, given systemically in chicks, produced behavioural stimulation, vocalization, increase in locomotor activity and ECoG desynchronization, with a significant fall in total and 0-3, 3-6, 6-9 and 9-12 Hz voltage power lasting approx. 3 h. Desipramine, an inhibitor of noradrenaline reuptake, produced in chicks behavioural and ECoG arousal, vocalization, pecking, escape responses and aggressive behaviour. In conclusion, the present experiments show that guanfacine sedative effects seem to be mediated predominantly via an activation of presynaptic alpha 2-adrenoceptors and suggest that arousal is due to stimulation of post-synaptic alpha 1-adrenoceptors.

Animals↗

Differential effects of the intraventricular administration of 6-hydroxydopamine on the induction of type II beta-tubulin and tyrosine hydroxylase mRNA in the locus coeruleus of the aging Fischer 344 rat.

Noradrenergic neurons of the locus coeruleus have been shown to respond to injury by increasing the synthesis of neurotransmitter (via the activation and induction of tyrosine hydroxylase, the rate-limiting catalyst in the production of catecholamines) and initiating compensatory axonal sprouting. However, this laboratory has recently described a significant deficit in the activation of tyrosine hydroxylase in the aged Fischer 344 rat, in contrast to the young and mature rat, following partial damage to cortical and hippocampal noradrenergic terminals induced by the neurotoxin 6-hydroxydopamine. To extend these observations, we measured changes in the relative levels of neuron-specific type II beta-tubulin and tyrosine hydroxylase mRNA in locus coeruleus neurons of 2, 12, and 24-month-old Fischer 344 rats following intraventricular infusions of 6-hydroxydopamine by using in situ hybridization histochemistry. These measures were used as markers of the responsiveness of these neurons to injury. 6-Hydroxydopamine treatment induced a persistent increase (at least 10 days) in the expression of type II beta-tubulin mRNA only in 2-month-old animals; this marker decreased in the 12 and 24-month-old animals. Relative levels of tyrosine hydroxylase mRNA increased in 2 and 12-month-old lesioned animals both 3 and 10 days post-treatment. In contrast, the induction of tyrosine hydroxylase mRNA in 24-month-old animals, seen three days post-treatment, was attenuated by 10 days. These data indicate that the capacity of locus coeruleus neurons to compensate for injury by either initiating a potential sprouting response or increasing their capacity to synthesize neurotransmitter is reduced in older animals.

Age Factors↗

Effects of intraventricular norepinephrine on preoptic-anterior hypothalamic electrical activity in the freely-moving rat: modulation by ovarian steroid hormones.

In freely-moving female rats the effects of intraventricular infusion of norepinephrine (NE) on multiunit activity (MUA) were examined in the Diagonal Band of Broca (DBB), medial preoptic area (MPOA) and anterior hypothalamic area (AHA), regions containing neurons producing luteinizing hormone-releasing hormone (LHRH). NE was infused at a dosage known to depress plasma LH levels in ovariectomized (OVX) rats and elevate plasma LH concentrations in OVX-estrogen-progesterone-primed (EBP) animals. It was found that in adult OVX rats MUA in the brain areas listed above was almost invariably inhibited by NE (20 of 23 cases or 87%; the other three cases showed no change in electrical activity). However, after priming with estrogen and progesterone only about one-third of the OVX-EBP rats gave an inhibitory response, with another one-third showing no change in MUA and the final one-third of the cases actually giving an excitatory MUA response to NE--the DBB neurons being the most positive in the regard. Thus it appears that responsiveness of LHRH and/or adjacent neurons to the modulatory action of NE may itself be modulated by the influence of gonadal steroids.

Animals↗

Differential effects of intraventricular luteinizing hormone releasing hormone (LH-RH) and norepinephrine on electrical activity of the arcuate nucleus in the proestrous rat.

Effects of intraventricular infusions of LH-RH and norepinephrine (NE) on the electrical activity of the arcuate nucleus were investigated in normally cycling proestrous rats. Under urethane anesthesia, recordings were made of amplitude-discriminated multiple unit spike activity and integated multiunit activity (MUA) in parallel with cortical EEG. Control infusions of saline (2 microliter, isotonic, pH 5.5) were ineffectual, but LH-RH (0.5 microgram) induced a significant increase in both multiunit spike activity and integrated MUA. While the response appeared to be continuous, statistical analysis revealed 2 phases: a quick rise which persisted for approximately 5 min, followed 15 min later by a longer-lasting elevation in activity. The onset of the 2nd increase corresponded with the attainment of peak values of pituitary LH output. Subsequent treatment with 20 microgram NE, on the other hand, resulted in a marked depression of activity. The fact that NE depresses arcuate neuronal activity at dose levels which cause the release of LH and that LH-RH increases activity within the same population of neurons, while possibly mediating an 'ultrashort-loop' negative feedback effect, suggest that this responsive component of the arcuate nucleus, perphaps the tuberoinfundibular dopaminergic system of neurons, is inhibitory to LH release.

Animals↗

Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats.

Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity, and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that pretreatment with basic fibroblast growth factor limits infarct size in a model of focal cerebral ischemia in vivo. Mature male Long-Evans rats received either continuous intraventricular infusion of basic fibroblast growth factor (1.2 micrograms/day; with or without heparin, added to stabilize the growth factor) or vehicle alone for 3 days before focal ischemic infarcts were made in the right lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intraoperative measurements of core temperature, arterial blood pressure and blood gases, blood glucose concentration, and hematocrit, and postoperative measurements of temperature revealed no differences among vehicle- versus basic fibroblast growth factor-treated animals. Twenty-four hours later, animals were killed, brains were removed and stained to visualize cortical infarcts, and infarct volume was determined by image analysis. Overall, we found a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (p < 0.01). This reduction was not enhanced by the addition of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Assessment of cerebral S100B levels by proton magnetic resonance spectroscopy after lateral fluid-percussion injury in the rat.

OBJECT: After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B. METHODS: Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an Sl00B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM-1 microM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p < 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague-Dawley rats (7 X 5 X 5-mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (approximately 200 ng/ml) through the intraventricular infusion of S100B increased the AUC of the S100B peak from 0.06 +/- 0.02 to 0.44 +/- 0.06 (p < 0.05), whereas serum S100B levels remained normal. Two hours after lateral fluid-percussion injury, serum S100B levels increased to 0.61 +/- 0.09 ng/ml (p < 0.01) and rapidly returned to normal levels, whereas the AUC of the S100B peak increased to 0.19 +/- 0.04 at 2 hours postinjury and 0.41 +/- 0.07 (p < 0.05) on Day 5 postinjury. CONCLUSIONS: Proton MR spectroscopy proves a strong correlation between the AUC of the S100B peak and S100B concentrations. Following experimental TBI, serum S100B levels increased for only a very short period, whereas cerebral S100B levels were increased up to Day 5 postinjury. Given that experimental data indicate that S100B is actively released following TBI, proton MR spectroscopy may represent a new tool to identify increased cerebral S100B levels in patients after injury, thus allowing its biological function to be better understood.

Animals↗

Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat.

Synaptic connectivity change is a consistent anatomical feature of memory formation and the possibility that this is mediated by a replay of neurodevelopmental events has been investigated by measuring change in neural cell adhesion molecule sialylation state during the acquisition and consolidation of a passive avoidance response in the adult rat. The avoidance response was always generated after two to three trials and the animals remained on the platform for the criterion time of 5 min. In all cases training was complete within 5-8 min. Change in sialylation state was monitored following intraventricular infusion of the 3H-ManNAc precursor at 4 hr prior to the reference point. No task-specific change in general glycoconjugate sialylation was apparent in hippocampal P2 pellets at increasing times following training. Increased sialylation state was observed only in neural cell adhesion molecule (NCAM) immunoprecipitates of hippocampal membrane fractions at 12 and 24 hr after training. Change in hippocampal sialylation state could not be attributed to an increased accumulation of NCAM as detected by an immunoabsorbent assay. Immunoblotting of antibody precipitated NCAM demonstrated the 3H-ManNAc to be incorporated into the synapse-specific, 180 kDa isoform of NCAM and a novel 210 kDa isoform. Immunoprecipitation and immunoblotting procedures with an antibody specific for a2-8-polysialic acid showed the 180 and 210 kDa isoforms to be polysialylated. The role of NCAM180 sialylation as a mechanism for synapse selection in information storage is discussed.

Animals↗

Spatial learning in the rat: impairment induced by the thiol-proteinase inhibitor, leupeptin, and an analysis of [3H]glutamate receptor binding in relation to learning.

Rats were given continuous intraventricular infusion of saline or the thiol-proteinase inhibitor leupeptin, via subcutaneously implanted osmotic minipumps, while being trained on a spatial learning water task using spaced trials. Leupeptin caused overnight forgetting during training, but performance eventually reached asymptote in both groups. A retention test conducted 48 h later to assess spatial memory revealed no significant group differences, but did cause, in saline-treated rats only, a disruption of subsequent retraining back to the correct spatial location. The groups showed no differences in Cl-dependent [3H]glutamate receptor binding to hippocampal or entorhinal cortex membranes subsequent to training. In a second experiment, normal rats trained on the same task also showed no differences in Cl-dependent [3H]glutamate binding relative to rats exposed to the water task but given random spatial position training and handled controls. The results are discussed in relation to the hypothesis of Lynch and Baudry (Science (1984) 224, 1057-1063) that a calcium-dependent thiol proteinase is involved in memory formation through its ability to modify glutamate receptor distribution and dendritic spine shape.

Animals↗

Behavioral effects of diltiazem injected into the paraventricular nucleus of the hypothalamus.

The calcium channel inhibitor diltiazem is widely used as a medication for cardiovascular diseases. Some side effects have been reported after its administration, including changes in activity (apathy or hyperactivity) and feeding behavior (anorexia). Previous experiments have found that local administration of various peptides into the paraventricular nucleus of the hypothalamus can have profound effects on these two behaviors. In the present study, effects of local infusions of diltiazem into the paraventricular nucleus on locomotor activity and food intake have been tested. A marked hyperactivity, greater than the hyperactivity caused by intraperitoneal injection of amphetamine was produced. Feeding behavior was not affected one hour after the infusions but intraventricular diltiazem infusions decreased feeding behavior. It is concluded that the paraventricular nucleus of the hypothalamus has an important role in the regulation of locomotor activity and that diltiazem can act at this level to produce behavioral changes.

Amphetamine↗

A search for the metabolic signal that sensitizes lateral hypothalamic self-stimulation in food-restricted rats.

Food deprivation and restriction increase the rewarding potency of food, drugs of abuse, and electrical brain stimulation. Based on evidence that the rewarding effects of these stimuli are mediated by the same neuronal circuitry, lateral hypothalamic self-stimulation (LHSS) was used to investigate the involvement of various metabolic signals in the sensitization of reward. In Experiment 1, glucoprivation with 2-deoxy-d-glucose (150 mg/kg, intraperitoneally (i.p.)) and lipoprivation with nicotinic acid (150 mg/kg, subcutaneously (s.c.)), individually and in combination, failed to affect the LHSS threshold in ad lib.-fed rats. These results suggest that signals associated with acute shortage of metabolic substrate do not sensitize reward. Because numerous responses to more prolonged negative energy balance are mediated by neuropeptide Y (NPY), the effect of exogenous neuropeptide Y upon LHSS was investigated in Experiment 2. Intraventricular infusion of orexigenic neuropeptide Y doses (2.0, 5.0, and 12.5 g), in ad lib.-fed rats, had no effect on LHSS threshold. In Experiment 3, other concomitants of prolonged negative energy balance--high circulating levels of free fatty acids (FFA) and beta-hydroxybutyrate (HDB)-were investigated. Nicotinic acid (250 mg/kg, s.c.), which suppressed serum HDB and FFA levels, had no effect on LHSS in food-restricted or ad lib.-fed rats. Mercaptoacetate (68.4 mg/kg, i.p.), which suppressed serum HDB levels and exacerbated the elevation of FFA levels, also had no effect. Thus, the brain reward system, if modulated by these substances, is not affected by transient, though marked, changes in their levels. To investigate the effect of a sustained increase in levels of FFA and HDB, a "ketogenic" diet was employed. Although this diet produced a fourfold increase in serum HDB levels, it had no effect on LHSS thresholds. Moreover, the failure of mercaptoacetate (68.4 mg/kg, i.p.) to decrease LHSS thresholds in these rats supports the conclusion that acute shortage of metabolic substrate does not sensitize reward. Other possible mechanisms of reward sensitization, including sustained decreases in circulating insulin and leptin and increases in corticosterone, are discussed.

Animals↗

The competitive NMDA antagonist AP5, but not the non-competitive antagonist MK801, induces a delay-related impairment in spatial working memory in rats.

Rats were trained to alternate responses on a discrete trial working memory task on a T-maze. In Experiment 1, the rats were then matched for choice accuracy and allocated to three treatment groups. These were: implantation of osmotic minipumps for intraventricular infusion of either (a) 15 mM D-2-amino-5-phosphonopentanoic acid (AP5) or (b) artificial cerebrospinal fluid (VEH); and an unoperated control group (UNOP). In Phase 1 we assessed alternation performance with a minimal delay between responses: the UNOP and VEH rats continued to choose accurately; the AP5 rats showed an impairment of choice accuracy, but recovered over days. In Phase 2 a 20-s delay between responses was enforced, and choice accuracy was assessed following injections either of saline or of Milacemide HCl (10 mg/kg). There was now a severe and enduring impairment of choice accuracy in the AP5 group, but Milacemide injections did not affect performance in any of the treatment groups. In Experiment 2 rats were trained in a similar way, and then given intraperitoneal injections of MK801 or of physiological saline in a within-subjects design and tested for T-maze performance with a minimal or a 20-s delay between responses. In the first Phase, MK801 was given 10-min before behavioural testing commenced; in the second Phase, it was given 28-40 min before behavioural testing commenced. The outcome depended critically on the time between drug injection and testing. There was a significant drug-induced impairment of choice accuracy in both Phases; but in Phase 1 there was no impairment in testing with a minimal retention interval and an impairment with a 20-s retention both retention intervals. We conclude that AP5, but not MK801, interferes with temporary memory storage in a delay-dependent manner.

2-Amino-5-phosphonovalerate↗

A cell-survival factor (N-acetyl-L-cysteine) alters the in vivo fate of constitutively proliferating subependymal cells in the adult forebrain.

The adult mouse brain contains a population of constitutively proliferating subependymal cells that surround the lateral ventricle and are the direct progeny of the neural stem cell. Constitutively proliferating cells divide rapidly; 6 days after labeling, 60% of their progeny undergo cell death, 25% migrate to the olfactory bulbs, and 15% continue to proliferate within the subependyma. We have intraventricularly infused a cell survival factor N-acetyl-L-cysteine (NAC), which is known to have survival effects without concomitant proliferative effects on cells in vitro, and examined the resulting fate of cells spared from the normally occurring cell death. NAC infusion for 5 days results in a five-fold increase in the number of retrovirally labeled subependymal cells compared to saline-infused controls. The increase in the number of subependymal cells is directly proportional to the amount of time during which NAC is present and is not due to increased proliferation. While NAC is able to keep all the normally dying progeny alive, the cells spared from death remain confined to the subependyma lining the lateral ventricles and do not migrate to the olfactory bulbs (one normal fate of constitutively proliferating progeny) or into the surrounding brain parenchyma. When animals survive for an additional 6 days following NAC infusion, the number of retrovirally labeled subependymal cells returns to control values, indicating that the continued presence of NAC is necessary for cell survival. These data suggest that preventing cell death is not sufficient to keep all of the progeny of these cells in a proliferative mode.

Acetylcysteine↗

Serotoninergic terminals: ultrastructure and synaptic interaction with catecholamine-containing neurons in the medial nuclei of the solitary tracts.

The ultrastructural morphology of serotoninergic terminals and their synaptic relation with catecholaminergic neurons were examined in the medial nuclei of the solitary tracts (m-NTS) using combined autoradiographic and immunocytochemical methods. Adult rats were pretreated with a monoamine oxidase inhibitor and subjected to a 2-hour intraventricular infusion of 50 nM tritiated 5-hydroxytryptamine (3H-5HT). At the termination of the infusion, the brains were fixed by aortic arch perfusion with a mixture of 4% paraformaldehyde and 0.5% glutaraldehyde. Coronal Vibratome sections through the NTS and more rostral raphe nuclei were immunocytochemically labeled with specific antiserum to serotonin or tyrosine hydroxylase and then processed for autoradiography. By light microscopy, concentrations of reduced silver grains indicating uptake of 3H-5HT usually paralleled the localization of peroxidase immunoreactivity for serotonin in neuronal perikarya of the rostral raphe nuclei and in varicosities in the brainstem. The 3H-5HT-containing varicosities were found throughout the medial and commissural portions of the NTS, where they were frequently associated with processes showing immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase. Ultrastructural examination of the m-NTS revealed that the silver grains for 3H-5HT were accumulated over axon terminals. The 5HT-labeled terminals contained a heterogeneous population of vesicles and formed both symmetric and asymmetric synapses with dendrites. The recipient dendrites were either, unlabeled or showed immunoreactivity for tyrosine hydroxylase. These findings support a direct serotoninergic modulation of catecholaminergic neurons within the rat m-NTS.

Animals↗

Non-invasive, quantitative assessment of the anatomical phenotype of corticotropin-releasing factor-overexpressing mice by MRI.

High resolution magnetic resonance imaging (MRI) was applied to quantify alterations in thymus and adrenal volumes, as well as body fat in genetically engineered corticotropin-releasing factor (CRF)-overexpressing mice. When compared to the organs in age-matched wild-type animals, the adrenals in CRF-overexpressing male mice were significantly enlarged and the thymus volume in females was significantly smaller. The fat content was significantly larger in CRF-overexpressing mice. The anatomical alterations observed in the MRI studies were in perfect line with post-mortem data (weights of organs). Furthermore, the observed interstrain differences are in agreement with recently published data on (i) the effect of continuous, intraventricular infusion of CRF in rats and (ii) the presence of atrophic adrenals in CRF-knockout mice. The present studies demonstrate that MRI can provide reliable measures of relatively small structures such as the adrenal glands and the thymus in mice. This makes MRI an attractive, non-terminal tool to monitor in laboratory animals, including transgenic mice, the consequence of continuous stress on relevant organs.

Adipose Tissue↗

The cholinergic system modulates kindling and kindling-induced mossy fiber sprouting.

In a previous study, our laboratory demonstrated that the intraventricular infusion of nerve growth factor (NGF) accelerated kindling rates and enhanced mossy fiber sprouting in the absence of noticeable kindling-associated neuronal loss. The purpose of the present study was to investigate whether these NGF effects were mediated via the cholinergic system. This study evaluated the effects of the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine on kindling rates and kindling-induced mossy fiber sprouting in adult rats. The results showed that pilocarpine accelerated kindling rates and enhanced kindling-induced mossy fiber sprouting in the CA3 region of the hippocampus, whereas scopolamine retarded kindling rates and blocked kindling-induced mossy fiber sprouting in the CA3 and IML regions. These findings suggest that the cholinergic system may contribute to the long-term structural and functional alterations that are characteristic of the kindled state. Moreover, these data provide support for the hypothesis that NGF infusions may mediate kindling and kindling-induced mossy fiber sprouting via regulation of the cholinergic system.

Animals↗

Serotonergic stimulation of prolactin secretion is inhibited by vasoactive intestinal peptide immunoneutralization in the turkey.

The neuronal mechanisms that govern prolactin (PRL) secretion in the turkey appear to involve monoaminergic systems. Considerable evidence indicates that serotonin (5-HT), acting centrally, is a potent stimulator of PRL secretion. This study, using birds actively immunized against VIP, tests the hypothesis that 5-HT stimulates PRL secretion by releasing vasoactive intestinal peptide (VIP). Nonimmunized turkeys were injected ip with saline, quipazine (5-HT agonist; 5 mg/kg), methysergide (5-HT antagonist; 8 mg/kg), or methysergide plus quipazine, and VIP-immunized birds were injected with saline or quipazine. Quipazine increased plasma PRL levels from 26.8 +/- 7.1 ng/ml at Time 0 to a peak value of 148.1 +/- 31.4 ng/ml 2 hr after infection. Pretreatment with methysergide or VIP-immunoneutralization abolished the PRL response to quipazine. Intraventricular infusion of 5-HT (1 nmol/min) caused plasma PRL to rise from a baseline of 16.3 +/- 2.6 ng/ml to 85.2 +/- 14.3 ng/ml after 30 min in nonimmunized control birds. Serotonin infusion did not induce PRL secretion in the VIP-immunized birds. These findings suggest that serotonergic stimulation of PRL secretion in the female turkey requires a functional VIPergic system.

Animals↗

Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin.

The immunotoxin 192-saporin, infused intracerebroventricularly into rats, destroys cholinergic neurons in the basal forebrain nuclei. Doses required for complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7-saporin, when infused intraventricularly into rats, destroys Purkinje cells in a pattern similar to that produced by 192-saporin, without affecting cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholinergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained in the multiple choice reaction time task and retested with more complex tasks after lesioning. They were also tested in the water maze, passive avoidance, acoustic startle, and open field. The OX7-saporin group exhibited changes in many tests suggesting hypermotility and sensory deficits. The 192-saporin groups differed from the OX7-saporin group when they displayed deficits in multiple choice reaction time tasks in which novel challenges were introduced, including sessions with a noise distractor, shortened and lengthened intertrial intervals, and use of nine instead of five sources of light stimulus. The 192-saporin groups showed no impairment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which effects of Purkinje cell loss predominate when 192-saporin is administered intraventricularly.

Animals↗