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At least 1,099 records · Page 61Linked to original sources
PubMed1999

GTS-21, a mixed nicotinic receptor agonist/antagonist, does not affect the nicotine cue.

Identification of nicotinic receptor subtypes involved in nicotine dependence is required for guiding the design of more selective antagonists capable of blocking the nicotine cue and nicotine self-administration. Due to the multiplicity of nicotinic receptors in the mammalian brain, selective agonists and antagonists are needed to assess the functional involvement of a particular subtype in vivo. Only recently have a few nicotinic receptor subtype-selective antagonists and agonists been identified. GTS-21 (also known as DMBX-anabaseine) is the only agent so far reported that selectively stimulates the alpha7 nicotinic receptor. Here GTS-21 was used to assess the possible mediation of the nicotine cue by this receptor subtype. Long-Evans rats were trained to discriminate between presession administration of 0.10 or 0.40 mg/kg (-)-nicotine bitartrate and its vehicle. GTS-21 did not substitute for nicotine, as all subjects consistently chose the vehicle lever after GTS-21 substitution. In another experiment, different doses of GTS-21 were administered prior to nicotine administration to investigate whether GTS-21 would antagonize the nicotine cue. Such was not the case. The lack of effect of GTS-21 upon the nicotine cue is consistent with the notion that the cue is mediated by nicotinic receptors other than the alpha7 receptor.

Alkaloids↗
PubMed1999

Influence of training paradigm on specificity of drug mixture discriminations.

Generalization to different drugs and drug mixtures has been examined in rats trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.

Animals↗
PubMed2000

Effects of SCH-23390 and raclopride on cocaine discrimination in male and female Wistar rats.

Male and female rats were trained to discriminate 10.0 mg/kg cocaine from saline in a two-lever discrimination task. Injection-appropriate responding was reinforced by food pellet presentation on a tandem random-interval 30-s fixed-ratio 10 schedule. Generalization testing was conducted in extinction 10 min following an injection of saline, 1.0, 3.0, 5.6, or 10.0 mg/kg cocaine. No differences in the generalization gradients and ED(50)s were observed between male and female rats. Following the determination of the cocaine generalization gradient, the dopamine D(1) antagonist SCH-23390 (0.01-0.10 mg/kg) and the dopamine D(2) antagonist raclopride (0.1-1.6 mg/kg) were administered (independently) prior to the injection of the training dose of cocaine (10.0 mg/kg). Cocaine-antagonism tests were conducted in extinction. It was found, for each dopamine antagonist, that as the dose increased, the percentage of cocaine-appropriate responding decreased. No sex differences were observed between these generalization gradients.

Animals↗
PubMed1984

Discrimination between aversive brain stimulations: effect of stimulation parameters.

Rats placed in a T maze were shown to be able to discriminate between two stimulations applied to one and the same brain site and inducing aversive effects of different magnitude. Discrimination occurred irrespective of whether the two stimulations differed in either intensity or frequency, and irrespective of whether they were applied to a medial hypothalamic or to a mesencephalic central gray site. Generalization experiments were performed in which either the stimulation parameter used to establish the discrimination or another parameter was varied. The results show that the animal's choice cannot be predicted on the sole basis of either the electrical charge/second applied or the escape latency induced.

Animals↗
PubMed1985

Effects of preexposure flavor concentration on conditioned aversion and neophobia.

In Experiment 1, 128 experimentally naive, water-deprived rats (Rattus norvegicus) received pretraining access to either 0.25 or 1.5% saccharin, distilled water, or 2.0% saline, followed either by a pairing of 0.25 or 1.5% saccharin with an intraperitoneal injection of 0.15 M lithium chloride (LiCl) or by a pairing of distilled water with LiCl. Preexposure to either saccharin concentration reliably reduced conditioned aversion effects to 0.25% saccharin, relative to that for preexposure to distilled water or saline. But only preexposure to 1.5% saccharin reduced aversion effects to that concentration. In Experiment 2, 48 naive, water-deprived rats received preexposure procedures as in Experiment 1. Afterwards, the rats were tested for neophobia to 0.25 or 1.5% saccharin. Neophobia was reliably greater to the 1.5% concentration. However, preexposure to either saccharin concentration obliterated evidence for neophobia to saccharin, relative to that following preexposure to distilled water or saline.

Animals↗
PubMed1985

Further evaluation of morphine aversion: maintenance of a taste aversion using a low, nonaversive morphine dose.

Previously, in an investigation of morphine-conditioned taste aversion (CTA), we found that limited preexposure to a low, nonaversive (non-CTA-inducing) dose of morphine (2.5 mg/kg) was as effective as preexposure to a higher, CTA-inducing dose (15 mg/kg) in blocking the formation of a subsequent morphine CTA. In the present study, we examined the capacity of this low, 2.5-mg/kg morphine dose to maintain a CTA initially induced by the 15-mg/kg dose. A standard CTA procedure was used. Results indicated that rats given three initial taste-drug pairings with 15 mg/kg morphine followed on subsequent pairing days by treatment with the low, non-CTA-inducing, 2.5-mg/kg dose continued to exhibit a strong CTA over 8 pairing days. A similar pattern was observed for animals continuing to receive taste-drug pairings with the 15-mg/kg dose. Animals receiving only one taste-drug pairing with the 15-mg/kg dose, followed on subsequent pairing days by 2.5-mg/kg conditioning, failed to show such a pattern of CTA. An intermediate CTA pattern was seen with animals conditioned with 15, 10, 5, and repeated 2.5-mg/kg doses over consecutive pairing days. These data suggest that exposure to a low dose of morphine, with no apparent CTA-inducing properties, is sufficient to maintain a previously established morphine taste aversion. Potential implications for understanding the apparent discriminative complexity of morphine's motivational properties are discussed.

Animals↗
PubMed2000

Conversion and storage of somatostatin are established before response to secretagogue stimuli in P19 neurons.

In mature neurons, neuropeptides are synthesized via limited proteolysis of propolypeptides by convertases. The bioactive peptides are then stored in secretory granules until they are released extracellularly upon the induction of a fusion between granules and the plasma membrane, in response to secretagogues. We used the mouse P19 embryonic carcinoma cells as a model to determine if the capacities to convert and store neuropeptides and to secrete them in a regulated fashion are established coordinately during neuronal differentiation. We have previously shown that both undifferentiated P19 cells and their neuronal derivatives express the largely distributed furin, PACE4 and PC5 convertases, whereas only neuronal derivatives express the neuroendocrine convertase PC2. In addition, undifferentiated cells displayed furin- rather than PC2-like converting capacities. The present work demonstrates that day 8 P19 neurons mainly convert prosomatostatin (proSS) to somatostatin-14 (SS-14) using HPLC and radioimmunoassay (RIA) analyses, indicating that P19 cells acquire PC2-like converting capacities as a consequence of neuronal differentiation. SS-14 was predominantly intracellular in neuronal cells which were shown to express several granins, markers of granules, by Western blotting. However, cell membrane depolarization with 50 mM K+, a general secretagogue stimulus, evoked the release of SS-14 by day 12, but not by day 8, P19 neurons. The results thus demonstrate that capacities to convert and store neuropeptides can be established before coupling of stimulus-secretion during neuronal differentiation.

1-Methyl-3-isobutylxanthine↗
PubMed1997

A computational model of the response of honey bee antennal lobe circuitry to odor mixtures: overshadowing, blocking and unblocking can arise from lateral inhibition.

Recent studies of learning about elements of odorant mixtures in honey bees identified several types of interactions between mixture components, such as overshadowing and blocking. The latter phenomenon in particular indicates at least a limited ability of subjects to identify the most salient element of a binary mixture. Here we show that the circuitry in the antennal lobes, the first neuropil in which synaptic interaction affects sensory processing, could give rise to both effects given the incorporation of modifiable synapses onto inhibitory circuitry. The neural model of the antennal lobe that we present incorporates identified cell types and includes a biologically realistic modulatory neuron with which modifiable Hebb-like synaptic interactions take place. A learning rule that incorporates modifiable connections from output (projection) neurons onto the modulatory neuron is sufficient to account for behavioral results on generalization and overshadowing. A second type of excitatory connection from the modulatory neuron onto local inhibitory interneurons is necessary to reproduce behavioral results from blocking and unblocking. We suggest that the neural representations of odor mixtures in the antennal lobe can be modified by previous exposure to one of the mixture components. These results provide testable hypotheses that will guide future behavioral and physiological analyses.

Algorithms↗
PubMed2000

A componential view of configural cues in generalization and discrimination in Pavlovian conditioning.

This paper describes three theoretical approaches to the representation of configural cues in generalization and discrimination in Pavlovian conditioning: that of the Rescorla-Wagner model, the Pearce model, and the authors' 'replaced elements' model. We summarize the results of a generalization experiment using the rabbit Pavlovian conditioned eyeblink response where animals were trained with cues A, AB, or ABC, and tested with A, AB, and ABC. The pattern of generalization decrement in testing supported the replaced elements model.

Animals↗