Neuroscience
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Comparative Study
A role for peripheral somatostatin receptors in counter-irritation-induced analgesia.
Our hypothesis is that peripheral somatostatin (SRIF) has a role in counter-irritation-induced analgesia. Our paradigm involves the reduction of nociceptive behaviors produced by primary noxious stimuli (formalin or complete Freund's adjuvant [CFA] in the rat hind paw) by a counter-irritating stimulus (capsaicin [CAP] in the tail or muzzle). Activation of peripheral SRIF receptors is key since an SRIF receptor antagonist cyclo-somatostatin (c-SOM) and SRIF antibodies in the hind paw attenuate the counter-irritation-induced analgesia of both formalin and more persistent CFA nociception. ⋯ Intraplantar naloxone has no effect on the counter-irritation analgesia indicating that SRIF is not activating opioid receptors. These results indicate that in addition to the classic central descending noxious inhibitory control systems that underlie counter-irritation-induced analgesia, there is a peripheral contribution arising from activation of SRIF receptors. Identifying a peripheral contribution of SRIF to mechanisms of counter-irritation analgesia offers opportunities for peripheral therapy.
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Comparative Study
Basolateral amygdala lesions impair both cue- and cocaine-induced reinstatement in animals trained on a discriminative stimulus task.
Drug-associated environmental cues can maintain drug use and contribute to relapse even after long periods of abstinence. We investigated the ability of sensory stimuli that signaled periods of reward availability to sustain cocaine self-administration and trigger the reinstatement of reward-seeking behavior. We demonstrate that lesions of the basolateral amygdala (BLA), a structure strongly implicated in attributing salience to environmental stimuli, significantly reduced the power of predictive cues to elicit reward-seeking behavior. ⋯ In sham-lesioned animals, cocaine and the DS, but not the CS or the S-, triggered reinstatement. BLA lesions abolished DS-induced reinstatement and significantly attenuated cocaine-induced reinstatement. These results demonstrate 1) that when tested under the same conditions, a discriminative cue which signals reward availability is a more robust trigger of reward-seeking than a Pavlovian CS which signals reward delivery and 2) that the BLA contributes to reinstatement in response to these discriminative cues.
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Comparative Study
Apolipoprotein E4 decreases whereas apolipoprotein E3 increases the level of secreted amyloid precursor protein after closed head injury.
Apolipoprotein E (apoE4) and head trauma are important genetic and environmental risk factors for Alzheimer's disease. Furthermore, apoE4 increases both the acute and chronic consequences of head trauma. The latter are associated with the deposition of amyloid-beta, which is particularly elevated in apoE4 subjects. ⋯ In contrast, CHI raised the cortical APP and APPs levels of the apoE3 transgenic mice but had no significant effect on those of the other mice groups. These animal model findings suggest that the acute, short-term pathological effects of apoE4 following CHI and the corresponding neuroprotective effects of apoE3 may be mediated by their opposing effects on the expression and cleavage of cortical and hippocampal APP. Similar isoform-specific interactions between apoE and APP may play a role in the acute, short-term effects of head trauma in humans.
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To gain insight into the role of melatonin and dopamine in retinal development, gene expression of two melatonin receptors, MT1 and MT2, as well as five dopamine receptors, D1, D2, D3, D4 and D5, in the rat eye was analyzed by reverse transcription-polymerase chain reaction across various developmental stages. MT1 transcript levels reached maximum levels at embryonic day (E) 16 and then decreased gradually until reaching adult levels by postnatal day (P) 14. MT2 transcript levels similarly peaked at E16, but then decreased dramatically until birth to its lowest levels, which were maintained throughout the postnatal period. ⋯ Gene expression of D1-like receptors, D1 and D5, showed a substantial increase to adult levels during the fetal period at E16 and E20, respectively. Transcript levels of D2-like receptors, D2 and D4, on the other hand, were not detected before birth but increased significantly to adult levels by P7 and P14, respectively. The present findings suggest the presence of unique developmental mechanisms by which transcription of various G protein-coupled receptors are regulated in the eye.
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Comparative Study
Neuropeptide Y, GABA and circadian phase shifts to photic stimuli.
Circadian rhythms can be phase shifted by photic and non-photic stimuli. The circadian clock, anatomically defined as the suprachiasmatic nucleus (SCN), can be phase delayed by light during the early subjective night and phase advanced during the late subjective night. Non-photic stimuli reset the clock when presented during the subjective day. ⋯ The administration of bicuculline during light exposure, before NPY microinjection did not alter the ability of NPY to attenuate light-induced phase delays and block photic phase advances. These results indicate that NPY attenuates photic phase shifts via a mechanism independent of GABA(A) receptor activation. Furthermore it is evident that NPY influences circadian clock function via differing cellular pathways over the course of a circadian cycle.