Neuroscience
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Repeated, intermittent exposure to the psychomotor stimulants amphetamine and cocaine induces a progressive and enduring augmentation of their locomotor-activating effects, known as behavioral sensitization, which is accompanied by similarly stable adaptations in the dendritic structure of cortico-striatal neurons. We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also results in long-lasting behavioral and morphological changes in mesocortical (medial prefrontal cortex) and ventral striatal (nucleus accumbens) neurons. Rats received two daily injections of either 5.0 mg/kg (+/-)-MDMA or saline vehicle, approximately 6 h apart, for 3 consecutive days, followed by 4 drug-free days for a total of 3 weeks. ⋯ In medial prefrontal cortex, the prelimbic subregion showed increased spine density on distal dendrites of layer V pyramidal neurons, while the anterior cingulate subregion showed a change in the distribution of dendritic material instead. Collectively, our results show that long-lasting locomotor sensitization to MDMA is accompanied by reorganization of synaptic connectivity in limbic-cortico-striatal circuitry. The differential plasticity in cortical subregions, moreover, suggests that drug-induced structural changes are not homogeneous and may be specific to the circuitry underlying long-term changes in drug-seeking and drug-taking behavior.
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The current study was conducted to examine the involvement of muscarinic acetylcholine receptors of the amygdala in morphine-induced state-dependent memory retrieval. Male Wistar rats implanted bilaterally with cannulas in the amygdala were submitted to a step-through type passive avoidance task, and tested 24 h after training to measure step-through latency. Post-training s.c. administration of morphine at the doses of 5 and 7.5 mg/kg impaired the memory on the test day, which was restored when the same doses of morphine were used as a pre-test drug. ⋯ In addition, no significant changes were seen in memory retrieval of the animals trained before saline treatment and tested following intra-amygdala microinjection of the same doses of scopolamine (0.0625, 0.125 and 0.25 microg/side). Bilateral microinjection of scopolamine into the amygdala reversed the pilocarpine-induced potentiation of the morphine response. In view of the known actions of the drugs used, the present data point to the involvement of amygdala muscarinic acetylcholine receptors in morphine-induced state-dependent memory retrieval.
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Adolescence may be a critical period for drug addiction. Young adolescent male rats have greater locomotor responses than adults after acute low dose cocaine administration. Further, repeated cocaine administration produces as much or more conditioned place preference but reduced locomotor sensitization in adolescents compared to adults. ⋯ Finally, there was a significant correlation between the expression of c-fos and zif268 in the adult striatum but not in adolescents. Our results suggest that the coordinated expression of transcription factors by cocaine continues to develop during adolescence. The immature regulation of transcription factors by cocaine could explain why adolescents show unique sensitivity to specific long-term behavioral alterations following cocaine treatment.
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Current theories of neuropathic hypersensitivity include an imbalance of supraspinal inhibition and facilitation. Our overall hypothesis is that the locus coeruleus (LC), classically interpreted as a source of pain inhibition, may paradoxically result in facilitation after tibial and common peroneal nerve transection (spared sural nerve injury--SNI). We first tested the hypothesis that non-noxious tactile hind paw stimulation of the spared sural innervation territory increases neuronal activity in the LC in male rats. ⋯ Lidocaine reduced all behavioral signs of neuropathic pain in a reversible manner, suggesting that the LC contributes to pain facilitation. We conclude that, in addition to its well-known inhibition of acute and inflammatory pain, the LC facilitates the development and maintenance of neuropathic pain in the SNI model. Further studies are needed to determine the facilitatory pathways emanating from the LC.
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Cerebral ischemia is a major cause of death and disability and may be a complication of neurosurgery. Certain anesthetics may improve recovery after ischemia and hypoxia by altering electrophysiological changes during the insult. Intracellular recordings were made from CA1 pyramidal cells in hippocampal slices from adult rats. ⋯ The average depolarization at 10 m of hypoxia with 33 microM propofol (-4.1 mV) was slightly but significantly different from that in untreated hypoxic tissue (-0.6 mV). Desflurane but not propofol improved recovery of the resting and action potentials in hippocampal slices after hypoxia, this improvement correlated with enhanced hyperpolarization and attenuated depolarization of the membrane potential during hypoxia. Our results demonstrate differential effects of anesthetics on electrophysiological changes during hypoxia.