Neuroscience
-
Using a rat relapse model, we have shown that infusion of a corticotropin-releasing factor (CRF) receptor antagonist into the median raphe nucleus (MRN) blocks footshock stress-induced reinstatement of alcohol seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured levels of c-fos mRNA in discrete nuclei of the rat brain following exposure to intermittent footshock, which was preceded by intra-MRN infusions of a CRF receptor antagonist, d-Phe CRF (0 or 50 ng). ⋯ Pretreatment with d-Phe CRF in the MRN selectively attenuated the increases in c-fos mRNA induced by footshock in the central nucleus of the amygdala (CeA). These findings are consistent with previous data on the important role for the CeA in stress-induced reinstatement of drug seeking. These results also suggest that inhibition of CeA activity may contribute to the blockade of alcohol-seeking induced by footshock that we have observed following injections of d-Phe into the MRN.
-
Comparative Study
Impaired long-term potentiation in obese zucker rats: possible involvement of presynaptic mechanism.
Electrophysiological investigation of basal synaptic transmission and synaptic plasticity in the CA1 region of the hippocampus was carried out in anesthetized obese Zucker rats (OZR). Comparison of the input/output curves of basal field excitatory postsynaptic potential indicates that these are similar in both the OZR and its lean counterpart suggesting that basal synaptic transmission is intact in the OZR. ⋯ Since post-tetanic potentiation and paired pulse facilitation, forms of short-term potentiation of presynaptic origin, are also severely impaired in the OZR, the results imply that impairment of CA1 hippocampal LTP in these obese rats may be due, in part, to impaired presynaptic function. The results emphasize the potential deleterious effect of obesity on learning and memory functions of the CNS.
-
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor that shares between 47 and 51% homology with other known bombesin receptors. The natural ligand for BRS-3 is currently unknown and little is known about the mechanisms regulating BRS-3 gene expression. Unlike other mammalian bombesin receptors that have been shown to be predominantly expressed in the CNS and gastrointestinal tract, expression of the BRS-3 receptor in the rat brain has previously not been observed. ⋯ Particularly strong immunosignals were observed in the cerebral cortex, hippocampal formation, hypothalamus and thalamus. Other regions of the brain such as the basal ganglia, midbrain and reticular formation were also immunopositive for BRS-3. In conclusion, our neuroanatomical data provide evidence that BRS-3 is as widely expressed in the rat brain as other bombesin-like peptide receptors and suggest that this receptor may also have important roles in the CNS, mediating the functions of a so far unidentified ligand.
-
Comparative Study
Impaired dendritic spine maturation in GABAA receptor alpha1 subunit knock out mice.
In this study we investigated the functional implications of GABAA receptor alpha1 subunit deletion on dendritic arborization and spine maturation in the visual cortex. This subunit is normally strongly upregulated during early postnatal development. ⋯ In contrast, dendritic arborization was not altered in these mice. We propose that an increased efficacy of the inhibitory synaptic transmission in the alpha1 knock out mice may lead to an enhancement of the outgrowth of filopodia around eye opening, but to a failure in spine maturation at later stages.
-
A delayed-matching spatial working memory protocol in a 5-arm maze was used to test the hypothesis of differential roles for central nicotinic and muscarinic cholinergic receptors in mediating task performance. In experiment 1, using a within subjects-repeated design, groups of C57Bl/6 mice, previously trained to criterion with a 4 h retention interval separating presentation and test phases, received i.p. injections of either saline, scopolamine (0.8 mg/kg), mecamylamine (8.0 mg/kg), or the combination of scopolamine and mecamylamine before re-testing. Injections were given either, a) 15 min pre-presentation or, b) 30 s, c) 15 min, d) 3 h 45 min post-presentation in order to differentially affect the acquisition, trace maintenance and recall phases. ⋯ Although the data show that central nicotinic and muscarinic antagonists both modulate working memory performance, they indicate first, that scopolamine-induced "amnesia" results, not from selective post-synaptic M1 muscarinic blockade but from indirect over-activation of nicotinic receptors. Second, the observation of high levels of retention although nicotinic and muscarinic receptors had undergone combined blockade during a large part of the retention interval is incompatible with the concept that test-induced activation of central cholinergic neurones mediates memory trace maintenance. Finally, taken with data from experiment 2, using a short (20 min) treatment-to-test interval, we conclude that central nicotinic receptors play a key role in attentional processes enabling working memory trace access during retrieval.