Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): interactions with reproductive status

Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long–Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20–22% lower than those fed a control diet containing adequate α-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D2-like receptors. Virgin females with decreased DHA also exhibited higher density of D1-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain

IntroductionDiet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females.MethodsHere, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high‐capacity runners; HCR) or low endurance exercise capacity (low‐capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions.ResultsLCR female rats have reduced mechanical sensitivity, higher intraepidermal nerve fiber density and TrkA‐positive epidermal axons, increased numbers of Langerhans and mast cells in cutaneous tissues, and a higher fat content despite similar overall body weights compared to female HCR rats. Sensory and motor nerve conduction velocities, thermal sensitivity, and mRNA expression of selected genes relevant to peripheral sensation were not different.ConclusionsThese results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.These results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139060/1/brb3780.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139060/2/brb3780_am.pd

G-Protein Activation by Neurokinin-1 Receptors Is Dynamically Regulated during Persistent Nociception

ABSTRACT Previous work has demonstrated that persistent nociception evokes increased neurokinin-1 receptor (NK-1) gene expression in the spinal cord dorsal horn of the rat within 2 h but has failed to elucidate the relationship between increased NK-1 gene expression at later time points and functional regulation of NK-1 receptor signaling. This study was undertaken to assess changes in NK-1 receptor mRNA levels in models of persistent inflammatory hyperalgesia and to relate them to changes in the functional coupling of NK-1 receptors to G-protein activity in the dorsal horn of the rat. Thus, unilateral intraplantar formalin or complete Freund's adjuvant was used to alter mechanical and thermal withdrawal thresholds in the inflamed paw. One to 96 h later, NK-1 receptor mRNA levels were quantified using solution hybridization-nuclease protection assays. Formalinevoked inflammation produced a 2-fold unilateral increase in NK-1 receptor mRNA levels apparent from 2 to 96 h postinjection. Histological sections of the lumbar cord from similarly treated rats were used to generate concentration-response curves using GTP␥S 35 functional binding assays stimulated by an NK-1 selective agonist. Results showed that formalin evoked a transient, bilateral decrease in the maximal functional response to 35% of control in the treated side at 24 h postinjection and as much as a 10-fold leftward shift in the EC 50 of the agonist at 12 to 96 h postinjection. These results provide novel evidence that peripheral nociceptive activation promotes a central mechanism of hyperalgesia through increased functional sensitivity of NK-1 receptors in the spinal cord dorsal horn

Representative images of Western blot analysis showing the effects of CFA-induced hyperalgesia on p-ERK1/2 and p-CREB protein levels in the rat hippocampus vs

<p><b>Copyright information:</b></p><p>Taken from "Neurokinin-1 (NK-1) receptor and brain-derived neurotrophic factor (BDNF) gene expression is differentially modulated in the rat spinal dorsal horn and hippocampus during inflammatory pain"</p><p>http://www.molecularpain.com/content/3/1/32</p><p>Molecular Pain 2007;3():32-32.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174921.</p><p></p> the ipsilateral dorsal horn of the spinal cord. Total protein from nuclear fractions of the tissue was immunoblotted with either monoclonal anti-phosphoERK1/2 (p-ERK1: M= 44 kDa; p-ERK2: M= 42 kDa) or monoclonal anti-phosphoCREB (p-CREB: M= 43 kDa) antibody. Tissue levels of constitutively expressed total ERK and total CREB proteins were used as loading controls. Proteins were visualized using secondary antibodies conjugated to HRP and a chemilluminescence detection system

Quantitative results of Western blot analysis showing the effects of CFA-evoked peripheral nociception on activation of CREB protein

<p><b>Copyright information:</b></p><p>Taken from "Neurokinin-1 (NK-1) receptor and brain-derived neurotrophic factor (BDNF) gene expression is differentially modulated in the rat spinal dorsal horn and hippocampus during inflammatory pain"</p><p>http://www.molecularpain.com/content/3/1/32</p><p>Molecular Pain 2007;3():32-32.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174921.</p><p></p> CFA increased phosphorylation of CREB in the ipsilateral dorsal horn at 24 h (single injection) and 21 days (three injections) post administration. Note that in the hippocampus the same treatment produced an opposite effect; p-CREB levels were significantly reduced at all time points. Optical density values are expressed as a ratio between the p-CREB (activated form) and total CREB (inactive form). Data are shown as % increase over sham control (n = 5); *p < 0.05 compared to control group (ANOVA and Student-Newman-Keuls' test)