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D G Spencer

Publications and source records attributed to D G Spencer.

At least 19 recordsLinked to original sources
PubMed1990

Stimulus properties of tiflucarbine: a novel antidepressant agent.

Tiflucarbine is a structurally novel antidepressant that binds at central serotonin (5-HT) binding sites. There is also evidence that this agent is both a 5-HT1 and a 5-HT2 agonist. To further characterize the serotonergic actions of this agent, tiflucarbine was evaluated in groups of rats trained to discriminate the 5-HT1A agonist 8-OH DPAT, the 5-HT2 agonist DOM, and the nonselective 5-HT agonist 5-OMe DMT from saline. Tiflucarbine resulted in partial generalization in the DOM-trained and in the 8-OH DPAT-trained animals. Although two-thirds of the animals were disrupted, 10 mg/kg of tiflucarbine resulted in stimulus generlization in the 5-OMe DMT-trained animals. It is concluded that tiflucarbine is most likely a nonselective 5-HT agonist.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1988

Behavioral and physiological detection of classically-conditioned blood pressure reduction.

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination setting. As the number of pairings increased, the anise/ethanol (but not the ethanol) stimulus, when given alone, came to both reduce blood pressure and to mimic clonidine's interoceptive stimulus to virtually the same extent as clonidine itself. Both responses induced by the conditioned stimulus (CS+; anise/ethanol odor) were antagonized by the noradrenergic alpha-2 receptor antagonist yohimbine at a dose that did not by itself influence blood pressure. These data support the hypothesis that activation of endogenous factors can be elicited by a CS, and that these factors may furthermore act agonistically at central alpha-2 receptors to reduce blood pressure in hypertensive animals.

Animals↗
PubMed1988

GTP effects in rat brain slices support the non-interconvertability of M1 and M2 muscarinic acetylcholine receptors.

GTP (guanosine-5'-triphosphate) markedly reduced high-affinity 3H-oxotremorine-M binding to M2 receptors on brain slices in autoradiographic experiments while 3H-pirenzepine binding to M1 receptors was largely unaffected. The distribution of M1 receptors so labelled was also not altered by GTP to include former M2-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M2 receptors to M1 receptors.

Animals↗
PubMed1988

Changes in septo-hippocampal projections after lateral entorhinal or combined entorhinal-raphé lesions as studied by anterograde tracing methods.

Septal and entorhinal projections to the hippocampus show a considerable overlap in their target structures in the molecular layer of the dentate gyrus (DG) and stratum lacunosum-moleculare of the cornu ammonis (CA). Employing anterograde tracing methods, it was investigated in which way the morphological pattern of the septohippocampal projections were influenced by lateral entorhinal cortex (LEA) lesions. Anterograde filling of neurons from soma to axonal terminals with Phaseolus vulgaris leucoagglutinin (PHA-L) revealed lesion-induced changes in innervation patterns in the DG but not in CA fields. LEA lesions provoke an impressive shift of septo-dentate projections from a predominant middle molecular layer innervation to the outer molecular layer, whereas septal projections to the CA remain unchanged. Comparison with concurrent acetylcholinesterase (AChE) staining and immunocytochemical demonstration of choline acetyltransferase (ChAT) confirm the cholinergic nature of this plasticity response. This response was equally strong in unilateral or bilateral damage to the LEA and was neither enhanced nor inhibited by simultaneous injury to the median raphé nuclei.

Acetylcholinesterase↗
PubMed1987

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transported Phaseolus vulgaris leucoagglutinin.

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.

Acetylcholinesterase↗
PubMed1987

Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine.

Male Wistar rats were trained to discriminate the interoceptive effects of 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT; 1.25 mg/kg, IP) from saline in a two-lever operant chamber. Following discrimination learning, the following drugs (with ED50 dose in mg/kg IP) dose-dependently generalized: lysergic acid diethylamide (LSD, 0.04), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.11), 6-methoxy-4-(dipropyl-amino)-1,3,4,5-tetrahydrobenz(c,d)indole hydrochloride (BAY R 1531, 0.15), 5-OMe-DMT itself (0.63), ipsapirone (TVX Q 7821, 2.7), and buspirone (3.8). The potencies of these drugs in generalization tests were best correlated with their binding affinities for the 5-HT1A serotonin receptor subtype (as measured by displacement of 3H-ipsapirone in the hippocampus). Drugs not, or only partially generalizing included quipazine, bufotenin, m-trifluoromethylphenylpiperazine (TFMPP), 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole succinate (RU 24969), citalopram, clomipramine, 1,4-dihydro-2,6-dimethyl-3-nitro-4(2-trifluoromethylphenyl)-pyridine-5- carboxylate (BAY K 8644), the buspirone metabolite 1-pyrimidinyl-piperazine (1-PP), methysergide, metergoline, and metitepine. Of the last three compounds with antagonistic activity at 5-HT receptors, as well as ketanserin, pizotifen, and ritanserin, only metitepine and pindolol could fully block the 5-OMe-DMT stimulus. Pizotifen blocked the generalization of quipazine fully, that of 5-OMe-DMT only partially, and that of ipsapirone not at all. These data indicate that the 5-HT1A receptor subtype is strongly involved in the transduction of the interoceptive discriminative stimuli induced by 5-OMe-DMT, with 5-HT2 agonism also playing a possible role.

Animals↗
PubMed1987

The interoceptive discriminative stimuli induced by the novel putative anxiolytic TVX Q 7821: behavioral evidence for the specific involvement of serotonin 5-HT1A receptors.

TVX Q 7821 is active in several behavioral models of anxiety in animals and has a high selective affinity for brain serotonin 5-HT1A receptors in binding assays. In order to determine if interaction with 5-HT1A receptors is important for some of the behavioral effects of this compound, 11 rats were trained to reliably discriminate the interoceptive stimuli induced by TVX Q 7821 (10 mg/kg, IP) from those of saline. Following discrimination acquisition, TVX Q 7821 administration resulted in drug-appropriate responding with an ED50 of 1.5 mg/kg, as did other substances with high affinity for the 5-HT1A receptor: 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, ED50 = 0.16 mg/kg), 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT, ED50 = 2.5 mg/kg), and buspirone (ED50 = 5.4 mg/kg). Anxiolytics not acting via the 5-HT1A receptor, like diazepam and pentobarbital, did not induce full TVX Q 7821-appropriate responses. In addition, non-selective 5-HT agonists and antagonists such as bufotenin, quipazine, and methysergide, as well as substances with high affinity for the 5-HT1B receptor (m-trifluoromethylphenylpiperazine, TFMPP; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate, RU 24969) did not substitute for TVX Q 7821. These data support a selective 5-HT1A mechanism of action in vivo for TVX Q 7821 and indicate the suitability of TVX Q 7821 for the investigation of behavioral correlates of the 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Detailed projection patterns of septal and diagonal band efferents to the hippocampus in the rat with emphasis on innervation of CA1 and dentate gyrus.

The detailed patterns of afferentation to the ammon's horn and dentate gyrus of the hippocampus in the rat were investigated employing the anterograde tracer Phaseolus vulgaris leuco-agglutinin (PHA-L) after punctate iontophoretic injections in the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB). The topographically ordered innervation pattern was different in the regio superior (or CA1) vs. the regio inferior (or CA3) and in the dorsal vs. ventral aspects of ammon's horn and dentate gyrus. The CA1 pyramidal and dentate granule cell layers in the dorsal hippocampus received afferent input almost exclusively from the VDB, whereas those cell layers in ventral hippocampus were supplied from both VDB and MS. The PHA-L labeled projecting fibers could be differentiated into two distinct fiber systems. One class of thick and coarse axons (tentatively called type I fibers) carried fewer but larger terminal boutons and were found to infiltrate the entire stratum oriens, dentate hilus, all layers of the regio inferior and the CA1 str. moleculare. A second, delicate thin (type II) fiber system provided with numerous and passant varicosities showed a much more restricted laminar innervation pattern and appeared to originate from areas in MS-VDB which are rich in AChE-positive neurons. The densest type II fiber networks could be observed in the CA1 subpyramidal and dentate supragranular zones, in the CA1 stratum lacunosum-moleculare and in the dentate middle third molecular layer. This laminar type II innervation pattern showed a remarkable coincidence with the reported distribution of cholinergic marker enzymes. The topographic and spatial organization of the projections described above will be discussed in relation to their possible functional significance.

Acetylcholinesterase↗
PubMed1986

Effects of N-ethylmaleimide on muscarinic acetylcholine receptor subtype autoradiography and inositide response in rat brain.

Chemical modification of brain muscarinic acetylcholine receptors (mAChr) with N-ethylmaleimide (NEM) has been employed to investigate mAChr-subtype distribution and mediation of the inositide response. 3H-Pirenzepine and 3H-oxotremorine-M were used to autoradiographically localize the M1- and M2-AChr subtypes, respectively, in brain slices. M1- and M2-AChr distribution were observed to be distinct from each other. The presence of 1 mM NEM selectively reduced the labeling of M2-, but not of M1-AChr. These data support the notion that NEM converts the high-affinity M2-AChr to a lower affinity state, without affecting the affinity of the M1-AChr. Also, regional analysis indicated that the M1- and M2-AChr subtypes were not interconvertible by NEM. NEM at 30 microM enhanced the carbamylcholine stimulated labeling of phosphatidic acid from 32Pi in nerve endings from rat forebrain, suggesting that the low affinity M2-AChr may mediate at least a part of the inositide response to cholinergic stimulation.

Animals↗
PubMed1986

Direct autoradiographic determination of M1 and M2 muscarinic acetylcholine receptor distribution in the rat brain: relation to cholinergic nuclei and projections.

The autoradiographic distributions of receptors with high affinity for [3H]oxotremorine-M (the M2 receptor) and [3H]pirenzepine (the M1 receptor) were studied in the rat brain. M1 receptors were seen in highest density only in telencephalic structures: cerebral cortex (layers I-II), hippocampus, dentate gyrus, medial and basolateral amygdala, nucleus accumbens and caudate/putamen. M2 receptors were detected throughout the brain, with highest levels observed in cerebral cortical layers III and V, forebrain cholinergic nuclei, caudate/putamen, various thalamic areas, inferior and superior colliculus, interpeduncular and pontine nuclei, brainstem cholinergic nuclei and cervical spinal cord regions. M2 receptors were found to be good markers for cholinergic cell groups and the majority of cholinergic projection areas, whereas M1 receptors were only found in a large sub-group of telencephalic cholinergic projection areas, and the pattern of distribution of receptors in these areas differed from that of M2 receptors. Scatchard analysis of [3H]oxotremorine-M binding to inferior collicular slices revealed one site with a dissociation constant (Kd) of 1.9 nM and a receptor density (Bmax) of 1.4 pmol/mg protein. Our data support the hypothesis that M1 and M2 receptors are physically distinct sub-types of the muscarinic acetylcholine receptor.

Acetylcholinesterase↗
PubMed1986

Behavioral impairments related to cognitive dysfunction in the autoimmune New Zealand black mouse.

The possibility that autoimmunological disorders involving neuronal constituents as autoantigens can result in measurable behavioral impairments prompted the behavioral analysis of the New Zealand black (NZB) mouse strain, known to have high levels of brain-reactive antibodies. Sensorimotor competence and performance in tasks requiring learning and memory were assessed in 7-10-month-old NZB and contrasted with those of CFW mice. The NZB mice showed pronounced deficits in performance of passive and active shock avoidance responses. These deficits could not be accounted for by the slight sensorimotor disadvantage of NZB mice relative to CFW mice. No difference between the two mouse strains was seen in passive avoidance behavior at 1.5 months of age. It is concluded that NZB mice display a behavioral deficit related to cognitive dysfunction and that autoimmune mechanisms may be involved in the etiology of this deficit. Such behavioral disturbances produced by an autoimmune mechanism may have relevance for the neurological declines observed in aging, since the incidence of autoimmune disorders increases markedly in old age.

Animals↗
PubMed1986

Employee voice and employee retention.

This study investigates the relationship between the extent to which employees have opportunities to voice dissatisfaction and voluntary turnover in 111 short-term, general care hospitals. Results show that, whether or not a union is present, high numbers of mechanisms for employee voice are associated with high retention rates. Implications for theory and research as well as management practice are discussed.

Communication↗
PubMed1985

The pattern of cortical projections from the intermediate parts of the magnocellular nucleus basalis in the rat demonstrated by tracing with Phaseolus vulgaris-leucoagglutinin.

The pattern and distribution of the cortical projections from intermediate parts of the cholinergic basal magnocellular nucleus were studied by anterogradely transported Phaseolus vulgaris-leucoagglutinin. This immunocytochemical tracing technique reveals the detailed morphology and distribution of efferents from this intermediate area in the nucleus basalis to the various areas and layers of cortex and amygdala. Major projections with a relatively high density of terminal boutons were found in layers I, II and VI of the frontal cortex, in layers V and VI of parietal and temporal areas, in the entire perirhinal and entorhinal cortices, and in the basolateral nucleus of the amygdaloid body. From the nucleus basalis area studied, few if any projections could be demonstrated to cingulate and occipital cortical regions.

Acetylcholinesterase↗
PubMed1985

Central cholinergic involvement in working memory: effects of scopolamine on continuous nonmatching and discrimination performance in the rat.

Rats were trained to stable baselines of lever pressing on a variable intertrial interval continuous nonmatching to sample schedule (CNM) or on an analogous discrimination schedule. Scopolamine reduced accuracy of CNM performance to a similar extent over the three intertrial (retention) intervals: 2.5, 5, and 10 s, results indicating that the drug did not affect the time-dependent process of retention in working memory. When baseline levels of performance accuracy were similar in the CNM and discrimination tasks (but stimulus discriminability was greater in the CNM task), scopolamine reduced accuracy equally in the two procedures. Effects of scopolamine on accuracy of noncorrection trial CNM performance were simulated by reducing stimulus discriminability; however, scopolamine disrupted CNM correction trial performance much more than did reductions in stimulus discriminability. It is concluded that scopolamine's effects on working memory are not limited to possible effects on stimulus discrimination: Scopolamine may also affect retrieval of response rules from reference memory.

Animals↗
PubMed1984

Task-specific tolerance to d-amphetamine.

Rats were trained concurrently on sweetened-milk drinking and bar-press-responding behavior, which alternated on a daily basis. Dose-response functions for d-amphetamine were determined before and after conditions of chronic treatment. When given before chronic treatment, d-amphetamine decreased both milk consumption and reinforcement received for lever-pressing in a dose-dependent manner. Subsequently, three conditions of chronic injection were established in which one group received saline, prior to both tasks, another group received d-amphetamine prior to drinking milk and saline prior to lever-pressing and the third group received d-amphetamine prior to lever-pressing and saline before drinking milk. The rats became tolerant to d-amphetamine in the task in which the drug had been administered chronically; however, the same rats showed no tolerance in the other task in which saline had been administered chronically. Tolerance to d-amphetamine was thus shown to be behaviorally specific.

Animals↗