Neuroscience
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Chronic opiate administration alters the expression levels of the stress-responsive peptide, corticotropin-releasing factor (CRF), in the bed nucleus of the stria terminalis (BNST). This brain region contains CRF receptors that drive drug-seeking behavior exacerbated by stress. We used electron microscopy to quantitatively compare immunolabeling of the corticotropin-releasing factor receptor (CRFr) and CRF in the anterolateral bed nucleus of the stria terminalis (BSTal) of mice injected with saline or morphine in escalating doses for 14 days. ⋯ In contrast, saline and morphine treatment groups showed no significant differences in the total number of CRF-immunoreactive axon terminals, or the frequency with which these terminals contacted CRFr-containing dendrites. This suggests that morphine does not influence axonal availability of CRF in the BSTal. The results have important implications for drug-associated adaptations in brain stress systems that may contribute to the motivation to continue drug use during dependence.
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Previous research in our laboratory has shown that damage to the amygdala in neonatal rhesus monkeys profoundly alters behaviors associated with fear processing, while leaving many aspects of social development intact. Little is known, however, about the impact of neonatal lesions of the amygdala on later developing aspects of social behavior. A well-defined phenomenon in the development of young female rhesus monkeys is an intense interest in infants that is typically characterized by initiating proximity or attempting to hold them. ⋯ However, following the birth of the infants, the amygdala-lesioned females showed significantly less interest in the infants than did control or hippocampus-lesioned females. They directed fewer affiliative vocalizations and facial expressions to the mother-infant pair compared to the hippocampus-lesioned and control females. These findings suggest that neonatal damage to the amygdala, but not the hippocampus, impairs important precursors of non-human primate maternal behavior.
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The encoding of reward-predictive stimuli by neurons in the nucleus accumbens (NAcc) depends on integrated synaptic activity from the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) afferent inputs. In a previous study, we found that single electrical stimulation pulses applied to the BLA facilitate mPFC-evoked spiking in NAcc neurons in a timing-dependent manner, presumably by a fast glutamatergic mechanism. In the present study, the ability of repetitive BLA activation to modulate synaptic inputs to NAcc neurons through dopamine- or N-methyl-D-aspartate (NMDA)-dependent mechanisms is characterized. ⋯ This was not attributable to mechanisms involving NMDA or dopamine D1, D2, D3 or D5 receptors, since blockade of these receptors did not affect the BLA-mediated depression. BLA-mediated depression was only evident when the BLA stimulation evoked spikes in the recorded neuron; thus, depolarization of the recorded neuron may be critical for this effect. The ability of the BLA to suppress mPFC-to-NAcc signaling may be a mechanism by which normal or pathologically heightened emotional states disrupt goal-directed behavior in favor of emotionally-driven responses.
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Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. ⋯ Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of venlafaxine in treatment of depression.
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Although skeletal pain can have a marked impact on a patient's functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague-Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15-16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP(+)) sensory nerve fibers, but not 200 kDa neurofilament H positive (NF200(+)) sensory nerve fibers in the periosteum. ⋯ These results suggest that both capsaicin-sensitive (primarily CGRP(+) C-fibers) and capsaicin-insensitive (primarily NF200(+) A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain.