Neuroscience
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The effect of the novel GABAc receptor antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl-phosphinic acid (TPMPA) on synaptic transmission and GABA-mediated responses was investigated with electrophysiological recordings from the in vitro spinal cord preparation of the neonatal rat. Bath-applied TPMPA (10 microM) had no effect on spinal reflexes evoked by dorsal root stimulation, on ventral root polarization level or amplitude of ventral root depolarizations induced by exogenously applied GABA (0.5 mM). TPMPA significantly attenuated the depressant action of GABA on spinal reflexes without changing responses induced by the GABA(A) receptor agonist isoguvacine (50 microM) or the GABA(B) receptor agonist baclofen (0.5-2 microM). ⋯ This bursting pattern, which is generated at the level of the interneuronal network, was significantly slowed down by TPMPA, which also increased the duration of individual bursts and the number of intraburst oscillations. These results suggest that in the neonatal rat spinal cord some functional GABAc receptors exist: their role was clearly unmasked following pharmacological block of GABA(A) (and glycine) receptors. Under these conditions GABAc receptors appeared to contribute to the excitation of spinal interneurons supporting rhythmic bursting activity.
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Arginine vasopressin peptide and messenger RNA expression were examined at the cellular level in the magnocellular and parvocellular neurons in the rat paraventricular nucleus after dehydration and rehydration, employing immunocytochemistry and in situ hybridization histochemistry on the same tissue sections. Most magnocellular vasopressinergic neurons of control animals expressed both vasopressin-like immunoreactivity and messenger RNA. However, neurons negative for vasopressin-like immunoreactivity but expressing messenger RNA were also detected, and their number increased during dehydration. ⋯ These findings suggest that magno- and parvocellular vasopressinergic neurons are differentially activated during dehydration/rehydration. Osmotic stimuli activate all magnocellular vasopressinergic neurons, but the effect is not simultaneous in all of these neurons. Parvocellular vasopressinergic neurons are also activated by the stress of dehydration which effect appears to last longer than in the magnocellular system.
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From a classical viewpoint, tolerance to analgesic effects of opiates refers to the decreased effectiveness of a given opiate following its repeated use. Despite much research, it has not been conclusively demonstrated in vivo that functional changes observed at the opioid receptor level in the responsiveness to opiates account for development of tolerance. An alternative hypothesis is that opioid receptors remain operative following repeated opiate administration but that opioid receptor activation rapidly induces a prolonged increase in pain sensitivity which opposes the predominant opiate analgesic effect following repeated opiate administration. ⋯ Herein we report that repeated once-daily heroin injections induced a gradual lowering of the nociceptive threshold which progressively masked a sustained heroin analgesic functional effect. MK-801 prevented such opiate-induced allodynia and thereby prevented development of an apparent decrease in the effectiveness of heroin. These results indicate that intermittent heroin administration induced a persistent increase in the basal pain sensitivity which, if not taken into account gives the impression of less analgesia, i.e. apparent tolerance.
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Streptozotocin-diabetic rats, an animal model for diabetes mellitus, show learning deficits and impaired long-term potentiation in the CA1-field of the hippocampus. The present study aimed to further characterize the effects of streptozotocin-diabetes on N-methyl-D-aspartate receptor-dependent long-term potentiation in the CA1-field, to extend these findings to N-methyl-D-aspartate receptor-dependent and independent long-term potentiation in other regions of the hippocampus and to examine effects on long-term depression. First, the effect of diabetes duration on long-term potentiation in the CA1-field was determined. ⋯ Expression of N-methyl-D-aspartate receptor-dependent long-term potentiation was impaired in the CA1-field and dentate gyrus and expression of N-methyl-D-aspartate receptor-independent long-term potentiation was impaired in the CA3-field. In contrast, expression of long-term depression was facilitated in CA1. It is suggested that this combination of changes in plasticity may reflect alterations in intracellular signalling pathways.
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Comparative Study
Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments.
The nucleus accumbens septi is the major target of mesolimbic dopamine neurons originating in the ventral tegmental area of the mesencephalon. Studies involving experimental manipulation of dopamine transmission by drugs and by lesions, as well as in vivo monitoring of extracellular dopamine concentrations, have provided evidence that the dopamine transmission of the nucleus accumbens plays an important role in behaviour motivated by conventional (e.g., food, sex) and drug reinforcers. Motivated behaviour is distinguished into an appetitive (preparatory/anticipatory) phase consisting of flexible response patterns intended to search and approach the reward itself, and a consummatory phase, consisting of fixed response patterns (eating, drinking, copulating, etc.) finalized to the utilization of the biological resources of the reward (caloric, metabolic, genetic, etc.). ⋯ Unpredicted consumption of Fonzies preferentially stimulated dopamine transmission in the shell as compared to the core. Appetitive food stimuli (perforated Fonzies-filled boxes) phasically stimulated dopamine transmission in the core but not in the shell and sensitized the dopamine response to feeding in the core but inhibited that in the shell. These clear-cut differences between nucleus accumbens shell and core suggest that phasic dopamine transmission in each compartment of the nucleus accumbens subserves different roles in motivated behaviour.