Biomedical subjects

C H Vanderwolf

Publications and source records attributed to C H Vanderwolf.

At least 37 records · Page 2Linked to original sources

PubMed1996

5-Hydroxytryptamine (5-HT) agonists: effects on neocortical slow wave activity after combined muscarinic and serotonergic blockade.

In freely-moving rats treated with a combination of reserpine (10 mg/kg, i.p.) and scopolamine (5 mg/kg, i.p.), neocortical low voltage fast activity (LVFA) associated with continuous multiunit activity (MUA) was abolished and replaced by 2-6 Hz large irregular slow activity (LISA) above 1.5 mV associated with a burst-suppression pattern of MUA. Administration of the monoamine oxidase inhibitor pargyline (50-100 mg/kg, i.p.) completely suppressed 2-6 Hz LISA and restored normal-appearing LVFA and continuous MUA. The 5-hydroxytryptamine (5-HT) receptor agonists quipazine (0.5-20 mg/kg, i.p.), (+/-)-DOI (0.1-5 mg/kg, s.c.), and buspirone (0.1-10 mg/kg, i.p.), but not 8-hydroxy-2-(di-n-propylamine) tetraline (8-OH-DPAT, 0.05-0.8 mg/kg, s.c.) and RU 24969 (1-30 mg/kg, i.p.), produced a partial suppression of 2-6 Hz LISA and restored some lower voltage activity (< 1 mV) above 6 Hz associated with continuous MUA. However, as opposed to pargyline, no receptor agonist tested restored continuous, normal-appearing LVFA. Even though agonists at 5-HT receptors can produce some activation of neocortical slow wave activity after combined cholinergic and serotonergic blockade, this effect is not equivalent to that observed after restoration of endogenous 5-HT transmission.

Animals↗

PubMed1996

Effect of colchicine-induced cell loss in the dentate gyrus and Ammon's horn on the olfactory control of feeding in rats.

Normal rats offered a choice between scented and unscented food pellets: (a) avoid food scented with toluene (an aromatic organic solvent) or 2-propylthietane (a component of the anal scent gland secretions of weasels); (b) prefer food scented with cadaverine (a diamine component of the odor of rotting flesh); but (c) neither prefer nor avoid food scented with butyric acid (a component of the odor of rancid butter) or caproic acid (a component of the odor of goats). Lesions of the dentate gyrus and CA1 (induced by local injections of colchicine) and/or the neocortex overlying the hippocampus produce a complex pattern of changes in these normal olfactory reactions, but do not affect the normal reaction to food flavored with sucrose or quinine. Cell loss in the hippocampal formation results in an abnormal aversion to butyric acid, in particular, but neocortical damage also alters the behavioral reaction to scented food. The results are consistent with the view that the hippocampal formation and the neocortex play differing roles in the olfactory control of behavior.

Animals↗

PubMed1996

Cholinergic activation of the electrocorticogram: an amygdaloid activating system.

In urethane-anesthetized rats, electrical 100-Hz stimulation of the basal amygdala changed neocortical electrical activity from 6-Hz or less large-amplitude, irregular slow activity to low-voltage fast activity (LVFA) including frequencies of above 10 Hz. A similar activating effect was seen in the hippocampus, where amygdala stimulation induced the appearance of rhythmical slow activity in the 2- to 6-Hz range. This activation of neocortical and hippocampal activity by amygdala stimulation was blocked by the cholinergic-muscarinic receptor antagonist scopolamine (0.5-5.0 mg/kg i.p.), but not by the peripheral antagonist methylscopolamine, in a concentration-dependent manner. In contrast, a blockade of ascending inputs from the midbrain to the neocortex by treatment with the serotonin-depletor p-chlorophenylalanine or cauterization of the rostral midbrain did not block neocortical LVFA to amygdala stimulation, even though the lesions abolished all LVFA to strong noxious stimuli such as tail pinches. Unilateral infusions of the local anesthetic lidocaine (1%) into the basal forebrain selectively blocked LVFA in the neocortex ipsilateral to the infusion. However, intracerebral or systemic administration of various excitatory amino acid antagonists (2-amino-5-phosphonovaleric acid, kynurenic acid, NPC 12626) was not effective in blocking LVFA to amygdala stimulation. An input from the amygdala to the basal forebrain cholinergic system appears to be one of multiple systems involved in the cholinergic activation of neocortical and hippocampal activity. Further, basal forebrain-cholinergic inputs to the cerebrum alone are sufficient to activate the electrocorticogram, as they sustain activation even in the absence of inputs from the mesencephalon.

Amygdala↗

PubMed1996

Anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT2 receptors. Short communication.

The general anesthetics urethane and chloral hydrate have profound anti-serotonergic effects both in the rat cortex in vivo and the rat aortic ring in vitro. The suggestion that these effects may be due to an action on 5-HT2 receptors was tested using ex vivo and in vitro [3H]ketanserin binding assays with membrane-enriched fractions from rat brain. Urethane did not alter [3H]ketanserin binding in the ex vivo assay. In the in vitro assay, urethane, chloral hydrate, and its active metabolite 2,2,2-trichloroethanol produced slight reductions (of 16%, 9%, and 18%, respectively) of [3H]ketanserin binding. These studies suggest that anti-serotonergic effects of urethane and chloral hydrate may not be mediated by a blockade of 5-HT2 receptors.

Anesthetics, Intravenous↗

PubMed1996

The role of brain noradrenaline in cortical activation and behavior: a study of lesions of the locus coeruleus, medial thalamus and hippocampus-neocortex and of muscarinic blockade in the rat.

Local injection of 6-hydroxydopamine in the locus coeruleus resulted in a 90% depletion of noradrenaline (NA) in the cerebral cortex as assessed by high-pressure liquid chromatography. This NA depletion had no effect on scopolamine-resistant hippocampal rhythmical slow activity and only an occasional effect on scopolamine-resistant neocortical low voltage fast activity. However, NE depletion resulted in a slight deficit in a behavioral swim-to-platform test and increased the deficit produced on the test by systemic treatment with scopolamine. Large surgical lesions of the medial thalamus or hippocampal formation plus posterior neocortex greatly increased the behavioral deficit produced by scopolamine. It is concluded that ascending noradrenergic projections play only a modest and possibly indirect role in the control of electrocortical activation and that a number of different brain lesions increase the behavioral impairment produced by central muscarinic blockade.

Animals↗

PubMed1996

The effects of different types of pre-training on the rat's retention performance in a swim-to-platform task following administration of scopolamine.

Previous research has found that centrally acting antimuscarinic drugs strongly impair the acquisition of a variety of learned behaviors in rats but have little effect on these same behaviors if training is given prior to drug treatment. We gave groups of rats different types of pre-training followed by treatment with scopolamine hydrobromide and subsequent testing on a simple swim-to-platform test. Factors such as practice in swimming without a platform to escape to, or learning to swim to a platform in a different apparatus or even to the test platform located in a different place did not protect the rats from the behavioral disruption produced by scopolamine. However, five training trials on the specific swim-to-platform task used in the retention test afforded almost complete protection against the effect of scopolamine. It appears that the protective effect of pre-training is highly specific and does not involve acquisition of some type of general rule which might survive antimuscarinic blockade.

Animals↗

PubMed1996

Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits.

A detailed behavioral analysis of water-maze acquisition showed that the N-methyl-D-aspartate (NMDA) antagonist NPC17742 and the muscarinic antagonist scopolamine caused sensorimotor disturbances in behaviors required for maze performances and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze in male rats. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under NPC17742 or scopolamine. The results indicated that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA or muscarinic activity may contribute to but do not appear to be essential for spatial learning in the water maze.

Amino Acids↗

PubMed1995

The neurotoxins colchicine and kainic acid block odor-induced fast waves and olfactory-evoked potentials in the dentate gyrus of the behaving rat.

It has previously been shown that the hilus of the dentate gyrus responds to odors (e.g. toluene) with a burst of fast waves and to electrical stimulation of the olfactory bulb with an evoked potential consisting of an early component immediately after the stimulus artifact, a second component with a 16-18-ms latency and additional late components. Spectral analysis revealed that odor-induced fast-wave bursts in the olfactory bulb and dentate gyrus both had a peak frequency of 15-20 Hz and were highly coherent. Unilateral intrahippocampal injections of colchicine or kainic acid were used in an attempt to destroy granule and pyramidal cells, respectively, while saline was injected on the opposite side as a control. Recordings from chronically implanted electrodes in the olfactory bulb and dentate gyrus demonstrated that saline had no effect while either neurotoxin abolished the odor-induced fast waves. In addition, the late 16-18-ms component of the dentate-evoked potentials after single-pulse stimulation of the olfactory bulb was abolished by either kainic acid or colchicine; the early dentate response, probably a volume-conducted olfactory response, was not abolished. Histological analysis indicated that kainic acid produced widespread non-specific damage in the hippocampal formation. Kainic acid-treated tissue exhibits a thinning of granule cell and molecular layers of the dentate gyrus as well as cell loss in CA3 and part of CA1.

Animals↗

PubMed1995

Urethane reduces contraction to 5-hydroxytryptamine (5-HT) and enhances the action of the 5-HT antagonist ketanserin on the rat thoracic aortic ring.

The general anesthetic urethane (ethyl carbamate) is widely used in electrophysiological in vivo experiments. However, its pharmacological effects are poorly understood. Here, the effects of urethane on in vitro contractile responses of the rat thoracic aortic ring preparation were investigated. Bath application of 5-HT produced a concentration-dependent contractile response (EC50 = 4.3 x 10(-6) M). Urethane (11.2 mM = 1 mg/ml) shifted the concentration-response curve (CRC) for 5-HT to the right (EC50 = 1.7 x 10(-5) M) and decreased the maximal contraction by 30.8%. The CRC for NA (EC50 = 7.2 X 10(-9)M) was also shifted to the right by urethane (EC50 = 1.4 X 10(-8)M), but the shift of the 5-HT-CRC was twice that of the NA-CRC (3.95 vs. 1.95). The CRC to KCl was shifted rightwards only slightly by urethane (ratio 1.27) and the maximal contraction to KCl was not affected. The CRC to replacement of CaCl2 (0.1-10 mM) to KCl-depolarized vessels in a Ca(2+)-free Krebs solution was unaffected by urethane. Ketanserin (10(-9)M) antagonized the contraction to 5-HT, and a combination of ketanserin and urethane was markedly more effective than either drug alone, decreasing the maximal contraction by 58%. Antagonism of NA contraction by prazosin (5 X 10(-8)M) was not increased by addition of urethane. The urethane dose used here approximates blood and brain concentrations required to produce anesthetic effects in mammals. It is possible that reductions in 5-HT transmission and, to a lesser extent, in NA transmission, but not blockade of Ca2+ or K+ channels, may contribute to the anesthetic effect of urethane. In addition, the action of the selective 5-HT2 antagonist ketanserin is clearly altered by urethane. These findings are important to consider when urethane is used for in vivo neurophysiological investigations, particularly when 5-HT mechanisms are involved.

Adrenergic alpha-Agonists↗

PubMed1995

Does a history of convulsions increase the amnestic effect of temporal region brain lesions?

Rats with surgical lesions of the hippocampal formation, amygdala, and nearby neocortex and pyriform cortex were impaired on a swim-to-platform test and on a passive avoidance test. These impairments were not increased by presurgical treatment with a series of 21 electroshock convulsions. To the extent that this rat preparation can be compared with human patients, the data suggest that a previous history of epileptic seizures does not increase the amnestic effect of temporal lobe lesions.

Amnesia↗

PubMed1995

Scopolamine blocks olfaction-induced fast waves but not olfactory evoked potentials in the dentate gyrus.

The presentation of some odorous materials such as xylene or toluene under the snout of rats has been shown to elicit 15-30 Hz fast-wave bursts in both the olfactory bulb and dentate gyrus. Electrical stimulation of the olfactory bulb elicits an evoked potential (latency of first peak is 16-18 ms) in the dentate gyrus. The present study demonstrates that scopolamine or atropine blocks toluene-induced fast-wave bursts in the dentate region and to a lesser degree in the olfactory bulb while leaving dentate gyrus electrically evoked potentials intact. Further, rhythmical burst stimulation of the olfactory bulb at fast-wave frequencies will elicit fast-wave-like oscillations in the dentate gyrus. These fast-wave-like events, unlike evoked potentials to single-pulse stimulation, are abolished after muscarinic receptor antagonism with atropine. Mechanisms at the olfactory bulb and dentate gyrus that produce fast oscillations may involve muscarinic cholinergic synapses while the simple transmission of single, non-oscillatory olfactory signals to the dentate gyrus does not.

Animals↗

PubMed1995

p-chlorophenylalanine-induced serotonin depletion: reduction in exploratory locomotion but no obvious sensory-motor deficits.

Para-chlorophenylalanine (PCPA) depletes central serotonin (5-hydroxytryptamine, 5-HT) by inhibiting tryptophan hydroxylase, an enzyme necessary for the synthesis of 5-HT. The effects of a wide range of PCPA doses (150-1000 mg/kg) on spontaneous exploratory locomotor activity in a novel environment, activity in running wheels and a number of sensory-motor capacities were examined. Administration of 1000 mg/kg PCPA reduced whole brain levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid to 9.4 and 8.2% of control levels, respectively. Treatment with PCPA produced a dose-dependent decrease in exploratory locomotion in an unfamiliar automated open field relative to vehicle-treated animals. Further, all measures of general, horizontal and vertical activity were suppressed by PCPA treatment. In contrast to previous work, hyperactivity of rats chronically housed in cages with running wheel access was not observed. In their home cages, some PCPA-treated rats exhibited hyper-reactivity to cutaneous stimulation. No other sensory-motor deficits were apparent. Previous theories of 5-HT function state that its action may be to inhibit motor activity or promote sleep. The present results challenge this view and suggest that 5-HT, at least in certain environments, may stimulate locomotor activity without directly controlling various sensory-motor capacities in rats.

Animals↗

PubMed1995

Some general anesthetics reduce serotonergic neocortical activation and enhance the action of serotonergic antagonists.

In urethane-anesthetized rats, neocortical LVFA induced by 100 Hz electrical stimulation of the median raphe area or by tail pinching was completely eliminated by a combination of scopolamine (5 mg/kg, IP) and p-chlorophenylalanine (500 mg/kg/day x 3, IP), providing evidence that LVFA is dependent on cholinergic-muscarinic and serotonergic inputs to the neocortex in urethane-anesthetized as well as in freely moving rats. The serotonergic receptor antagonists ketanserin and methiothepin (1-10 mg/kg, IP) also produced a dose-dependent blockade of LVFA in urethane-anesthetized rats, and eliminated virtually all LVFA when combined with scopolamine. A combination of diethyl ether anesthesia and scopolamine completely eliminated all neocortical LVFA without additional antiserotonergic treatment, and a combination of chloral hydrate anesthesia and scopolamine similarly blocked all LVFA in about 50% of the rats tested. In the remaining chloral hydrate-anesthetized rats, the residual LVFA could be eliminated by the serotonergic antagonist ritanserin (10 mg/kg, IP). As shown previously, in nonanesthetized rats treated with scopolamine, LVFA can be maintained by a serotonergic input to the neocortex. The present data suggest that some general anesthetics reduce or completely abolish this serotonergic LVFA. Further, the serotonergic antagonists used here exert much stronger antiserotonergic effects in rats anesthetized with urethane or chloral hydrate than in freely moving rats. Therefore, studies of serotonergic transmission or antagonist action, especially in the neocortex, in anesthetized rats may not be applicable to the waking state.

Anesthetics, General↗

PubMed1994

Components of weasel and fox odors elicit fast wave bursts in the dentate gyrus of rats.

Previous work has shown that olfactory stimulation with toluene, xylene and other organic solvents elicits a burst of 15-30 Hz fast waves in the dentate gyrus of male rats. Other odorous substances including food, rat vaginal secretions and rat excrement were much less effective. In the present study we confirm that water, ammonia, rat food, rat cage litter and the presence of a conspecific did not reliably elicit dentate fast wave responses but that toluene and methyl methacrylate were very effective. We further show that both 2-propylthietane, which is a component of weasel gland secretions, and trimethyl thiazoline, an ingredient of fox droppings, elicited dentate fast waves as effectively as toluene and methyl methacrylate and that putrescine, cadaverine, butyric acid, caproic acid and indole were ineffective by comparison. Similarly, orally administered solutions of acetic acid, quinine, sodium chloride and sucrose were ineffective. These findings raise the possibility that the dentate fast waves elicited in the rat may be part of a cerebral response to the odor of a potential predator, such as the weasel or fox.

Animals↗

PubMed1994

Dentate gyrus and olfactory bulb responses to olfactory and noxious stimulation in urethane anaesthetized rats.

Recent research has shown that olfactory stimuli such as toluene vapor, but not visual, auditory, tactile or gustatory stimuli, elicit a burst of fast waves (15-30 Hz) in the hilus of the dentate gyrus in waking rats. In urethane-anaesthetized rats, toluene odors elicit similar fast waves. The present study shows that noxious stimulation (tail clamp) produces a blockade of spontaneous slow waves (1-12 Hz) in the hilus of the dentate gyrus but does not increase fast wave activity in urethane-anaesthetized rats. This slow wave blockade, which resembles neocortical activation, is independent of olfaction since it is not affected by tracheotomy. In contrast, tracheotomy abolishes the fast wave response to toluene presentation to the snout unless the toluene vapor is drawn into the nasal passages by suction at the rostral end of the severed trachea. Both the toluene odor-induced fast wave and the tail clamp-induced activation responses are abolished by scopolamine hydrobromide (5.0 mg/kg, i.p.) but not by scopolamine methyl bromide (5.0 mg/kg, i.p.) which does not cross the blood-brain barrier. However, evoked potentials elicited in the dentate hilus by single pulse stimulation of the olfactory bulb are not blocked by scopolamine in urethane-anaesthetized rats. The results suggest that several different types of electrical activity in the hippocampal formation are mediated by cholinergic inputs and that the dentate gyrus plays a role in olfaction.

Anesthesia↗

PubMed1994

Histamine does not play an essential role in electrocortical activation during waking behavior.

Intraperitoneal injection of alpha-fluoromethylhistidine (alpha-FMH; 200 mg/kg), a specific inhibitor of histidine decarboxylase produced a severe depletion of neocortical and hippocampal histamine 3 h later as determined by a radioenzymatic assay. This treatment had no obvious effect on either low voltage fast activity (LVFA) in the neocortex or on rhythmical slow activity (RSA) in the hippocampus during an 8 h recording period during the rats' light cycle. Scopolamine-sensitive LVFA, scopolamine-resistant LVFA and scopolamine-resistant hippocampal RSA all appeared unaffected. This suggests that any contribution histamine makes to electrocortical activation is probably indirect, acting via other transmitter systems.

Animals↗

PubMed1994

Food carrying in rats is blocked by the putative anxiolytic agent buspirone.

The effects of the putative anxiolytic agent buspirone on food-handling behavior of laboratory rats were investigated. Rats trained to travel from a covered shelter to a food source were provided with food pellets of six sizes. Smaller pellets were eaten at the exposed food source, whereas larger pellets were carried back to the shelter for consumption. Subcutaneous administration of buspirone hydrochloride (0.2-2.0 mg/kg) reduced carrying of larger food pellets in a dose-dependent manner. Instead, these pellets were also eaten at the exposed food source. Carrying was maximally suppressed 1 h after drug administration. Handling of smaller pellets, travel times, and eating times were not affected by buspirone. Similar results have previously been obtained with diazepam. Buspirone appears to exert its effects through 5-HT1A and/or dopamine receptors, whereas diazepam interacts with benzodiazepine receptors. Thus, manipulations of distinct transmitter systems may have similar behavioral consequences on the food carrying responses of rats.

Animals↗

PubMed1994

The behavioral neurobiology of learning and memory: a conceptual reorientation.

Research on the neurobiology of learning and memory has been guided by two major theories: (i) memory as a psychological process and (ii) memory as a change in synaptic neural connectivity. It is not widely recognised that not only are these theories different but, moreover, they are fundamentally incompatible. Confusion concerning basic concepts in the learning and memory field in mammals has lead to the creation of an extensive but often inconclusive experimental literature. However, one important conclusion suggested by recent work in this field is that experience-dependent changes in neural connectivity occur in many different brain systems. Particular brain structures, such as the hippocampus, do not play any uniquely important role in experience-dependent behavior. Research in learning and memory can be best pursued on the basis of biological studies of animal behavior and a cellular approach to brain function.

Animals↗