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Andrew J. Lawrence - One of the best experts on this subject based on the ideXlab platform.
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Effect of Chronic Ethanol and Withdrawal on the m-Opioid Receptor- and 5-Hydroxytryptamine1A Receptor-Stimulated Binding of [35S]Guanosine-59-O-(3-thio)triphosphate in the Fawn-Hooded Rat Brain: A Quantitative Autoradiography
2016Co-Authors: Feng Chen, Andrew J. LawrenceAbstract:Previous studies have shown that chronic ethanol influences the density of central m-opioid receptors and serotonin1A (5-hydroxytryptamine1A) receptors. To determine whether the functional coupling of these two receptors to G proteins in the Rat brain, particularly in mesocorticolimbic regions, is affected by ethanol, receptor-mediated [35S]guanosine-59-O-(3-thio)-triphosphate ([35S]GTPgS) binding stimulated by [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) or L694,247 was used. By quantitative autoradiography, receptor-medi-ated [35S]GTPgS binding activated by the two agonists was mapped throughout brain sections at the level of the nucleus accumbens and hippocampus from groups of alcohol-pre-ferring Fawn-Hooded (FH) Rats after different ethanol con-sumption paradigms. Significant DAMGO (m-opioid receptor agonist)-stimulated binding of [35S]GTPgS was obtained in the striatum, nucleus accumbens, and lateral septum, whereas L694,247 (5-hydroxytryptamine1A/1B/1D receptor agonist)-stimulated binding of [35S]GTPgS was observed in the lateral septum, amygdala, and cingulate cortex. Chronic ethanol self-administRation significantly reduced DAMGO-stimulated [35S]GTPgS binding in the nucleus accumbens (219%), lateral septum (215%), and striatum (223%), which recovered toward control levels after ethanol withdrawal. However, chronic ethanol, as well as ethanol withdrawal, failed to produce any significant alteRation in L694,247-stim-ulated [35S]GTPgS binding in all tested brain regions. The region-specific and receptor-specific alteRation of agonist-stimulated [35S]GTPgS binding suggests that the change of functional coupling of m-opioid receptors to G proteins in-duced by chronic ethanol drinking may have a pathophysi-ological role in the consequences of ethanol consumption. Opioidergic and serotonergic neurotransmissions in the central nervous system have been shown to play significant roles in alcohol abuse or alcoholism (Gianoulakis, 1993
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modulation of high alcohol drinking in the inbred Fawn Hooded fh wjd Rat strain implications for treatment
Addiction Biology, 2006Co-Authors: David H Overstreet, Feng Chen, Amir H Rezvani, Michael S Cowen, Andrew J. LawrenceAbstract:The Fawn‐Hooded Rat (FH/Wjd) is an inbred alcohol-preferring Rat strain, unlike most of the other strains that were selectively bred for high alcohol intake and preference. It was chosen for study some 16 years ago because of a reported mutation that disrupted platelet serotonin function. Although the FH/Wjd Rat has high alcohol intake ( > 5 g/kg/day) and preference ( > 65%), interbreeding with an alcohol-non-preferring inbred strain suggested that these measures are unrelated to the serotonin abnormality. Similarly, the exaggeRated immobility of the FH/Wjd Rats in the forced swim test did not correlate with the high alcohol intake. Many compounds have been tested in the FH/Wjd Rats after both acute and chronic treatment and a substantial number of them have proved effective. However, as the case with opiate antagonists, tolerance to the effects of the drug can develop. An up-regulation of opioid receptors accompanied the chronic treatment and this mechanism may account for the development of tolerance. Tolerance to opiate antagonists has also been demonstRated in two of the selectively bred alcohol-preferring Rat lines, but it is unknown whether this process may contribute to the relapses seen in individuals being treated with naltrexone. Other drugs that reliably decrease alcohol intake in the FH/Wjd Rats include the 5-hydroxytryptamine-2A receptor antagonist, amperozide, the mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and herbal derivatives such as ibogaine, St. John’s wort and kudzu extract. Thus, studies in the FH/Wjd Rat have led to the discovery of a wide variety of targets for the development of novel agents to treat alcoholism. The fact that several of these drugs were shown to reduce alcohol intake in some of the selectively bred alcohol-preferring Rat lines and/or alcohol-preferring vervet monkeys increases our confidence that they are good candidates for further development.
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Chronic corticotropin-releasing factor type 1 receptor antagonism with antalarmin regulates the dopaminergic system of Fawn-Hooded Rats.
Journal of neurochemistry, 2005Co-Authors: Andrew J. Lawrence, Katie Card, Daniel James Lodge, Clare L. Parish, Feng Chen, Elena Krstew, David Finkelstein, Malcolm K. HorneAbstract:Corticotropin-releasing factor is a neuropeptide associated with the integRation of physiological and behavioural responses to stress and also in the modulation of affective state and drug reward. The selective, centrally acting corticotropin-releasing factor type 1 receptor antagonist, antalarmin, is a potent anxiolytic and reduces volitional ethanol consumption in Fawn-Hooded Rats. The efficacy of antalarmin to reduce ethanol consumption increased with time, suggestive of adaptation to reinforcement processes and goal-directed behaviour. The aim of the present study was to examine the effects of chronic antalarmin treatment on reward-related regions of Fawn-Hooded Rat brain. Bi-daily antalarmin treatment (20 mg/kg, i.p.) for 10 days increased tyrosine hydroxylase messenger RNA expression throughout the ventral mesencephalon. Following chronic antalarmin the density of dopaminergic terminals within the basal ganglia and amygdaloid complex were reduced, as was dopamine transporter binding within the striatum. Receptor autoradiography indicated an up-regulation of dopamine D2, but no change in D1, binding in striatum, and Golgi-Cox analysis of striatal medium spiny neurones indicated that chronic antalarmin treatment increased spine density. Thus, chronic antalarmin treatment modulates dopaminergic pathways and implies that chronic treatment with drugs of this class may ultimately alter postsynaptic signaling mechanisms within the basal ganglia.
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the effect of chronic ethanol consumption and withdrawal on μ opioid and dopamine d1 and d2 receptor density in Fawn Hooded Rat brain
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Elvan Djouma, Andrew J. LawrenceAbstract:Previous studies have implicated the dopamine and opioid systems in the induction and maintenance of ethanol consumption. This study investigated, in alcohol-preferring Fawn-Hooded (FH) Rats, whether chronic free-choice ethanol consumption and subsequent withdrawal cause alteRations in central mu-opioid, dopamine D(1), and D(2) receptor density using autoradiography. FH Rats were given a free choice between a 5% ethanol solution and tap water (n = 25) and displayed a mean ethanol consumption of 5.6 g/kg/day. A parallel group of FH Rats (n = 5) only had access to tap water. Rats were then withdrawn from ethanol for 0, 1, 2, 5, or 10 days and killed by cervical dislocation and decapitation. Increases in mu-opioid receptor density were observed in the nucleus accumbens and ventral tegmental area upon withdrawal compared with the ethanol naive group. In the lateral amygdala, binding in all withdrawal groups was significantly different from the ethanol naive FH Rats, and also from the chronic ethanol Rats. An increase in dopamine D(1) receptor density was observed in the substantia nigra, pars reticulata in the 5- and 10-day withdrawal groups compared with ethanol naive. Accumbal dopamine D(2) receptor density (+25-30%) increased in the 10-day withdrawal group compared with both naive and chronic ethanol groups. These findings demonstRate that the opioid and dopamine systems are susceptible to modulation by chronic ethanol consumption and withdrawal in the FH Rat. Furthermore, although acute ethanol withdrawal results in modulation of mu-opioid receptors, effects on dopamine receptors are delayed and only become evident 5 to 10 days after withdrawal.
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compaRative analysis of the central cck system in Fawn Hooded and wistar kyoto Rats extended localisation of cck a receptors throughout the Rat brain using a novel radioligand
Regulatory Peptides, 2001Co-Authors: Daniel J Lodge, Andrew J. LawrenceAbstract:Abstract The neuropeptide cholecystokinin has been implicated in the actions of a number of central processes including anxiety and reward. For this reason, the aim of the present study was to compare the density of CCK-A and -B receptors and the mRNA encoding preproCCK throughout the brains of an alcohol-preferring (Fawn Hooded) Rat strain with that of a non-alcohol-preferring (Wistar Kyoto) strain of Rat. Our study revealed significant differences with regard to the central CCK system of the FH compared to the WKY Rat, including differences in CCK-A receptor binding throughout the dorsal medulla, and altered CCK-B binding density throughout the cerebral cortex and reticular nucleus of the thalamus. The most striking result, given the altered behavioural phenotype of the FH Rat, was the 33% lower density of CCKmRNA measured throughout the ventral tegmental area of the FH Rat when compared to the WKY. This study also reports on a protocol to utilise a novel radioligand, [ 125 I]- d -Tyr-Gly-A-71378, for autoradiographic detection of CCK-A receptors throughout the Rat brain. As previously reported, CCK-A receptors were located throughout the area postrema, interpeduncular nucleus and nucleus tractus solitarii; however, binding to CCK-A receptors was also visualised throughout the medial pre-optic area, the arcuate nucleus and the circumventricular regions of the ventral hypothalamus, regions known to contain CCK-A receptors but which were previously undetectable using autoradiography in Rat brain.
A P Provoost - One of the best experts on this subject based on the ideXlab platform.
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renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn Hooded Rat
American Journal of Physiology-renal Physiology, 2010Co-Authors: Peter Ochodnický, A P Provoost, Robert H Henning, Hendrik Buikema, Dick De Zeeuw, Richard P E Van DokkumAbstract:It is unknown whether generalized vascular dysfunction precedes the development of kidney disease. Therefore, we studied myogenic constriction and endothelium-mediated dilatory responses in two inb...
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altered renal hemodynamics and impaired myogenic responses in the Fawn Hooded Rat
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1999Co-Authors: Richard P E Van Dokkum, A P Provoost, Howard J Jacob, Chengwen Sun, Richard J RomanAbstract:The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contribu...
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tubuloglomerular feedback and prolonged ace inhibitor treatment in the hypertensive Fawn Hooded Rat
Nephrology Dialysis Transplantation, 1998Co-Authors: G H Verseput, A P Provoost, B B Braam, H A KoomansAbstract:Background. The spontaneously hypertensive Fawn-Hooded (FHH) Rat develops severe glomerulosclerosis with ageing. The afferent arteriolar resistance is low, resulting in a strongly elevated glomerular capillary pressure (P GC ). Methods. Afferent arteriolar resistance is under the control of the tubuloglomerular feedback (TGF) system, and we studied whether young FHH Rats, i.e. at a stage when only mild glomerulosclerosis was present, have diminished TGF responsiveness. Results. Maximum TGF-mediated decreases in stop-flow pressure in response to late proximal perfusion with artificial tubular fluid were 9.0 ± 1.0 mmHg, a value not different or even slightly lower than observed in normal Rats. P GC was 59.9 ± 1.2 mmHg and the estimated P GC at half-maximal activation of the TGF system (opeRating P GC ) was 54.5±0.8 mmHg at 11 weeks of age (n = 11), a value higher than observed in normal Rats. The second question of the present study concerns the effect of chronic angiotensin-I-converting enzyme inhibitor (ACE-i) administRation on P GC . ACE-i, by reducing angiotensin II (Ang II) availability, diminishes TGF responsiveness, which would offset the beneficial effect on P GC under normal flow conditions to the macula densa. Maximum TGF responses were 8.9 ± 1.0 and 17.5 ± 1.5 mmHg in 11- and 26-week-old Rats that had been treated with the ACE-i lisinopril in the drinking water started when the animals were 7 weeks of age. P GC was 44.3 ± 1.2 (n = 9) and opeRating P GC was 40.1 ± 1.6 mmHg (n=9) at 11, values significantly lower than in untreated Rats. Values remained lower in the 26-week-old treated animals and were 40.9 ± 0.8 and 32.6 ± 1.1 mmHg. Conclusions. (1) the TGF system in this model of spontaneous hypertension and glomerulosclerosis is intact, despite the fact that the FHH Rat has a characteristically low afferent arteriolar resistance as compared to other hypertensive Rats; (2) the Rat displays a normal or even enhanced function of the TGF system following prolonged administRation of the ACE-i lisinopril. The latter finding indicates that the reduction of P GC achieved by the ACE-i is not offset by a concomitant attenuation of TGF function.
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angiotensin converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive Fawn Hooded Rat
Journal of The American Society of Nephrology, 1997Co-Authors: G H Verseput, A P Provoost, B B Braam, Jan J Weening, H A KoomansAbstract:The spontaneously hypertensive Fawn-Hooded Rat (FHH) develops acceleRated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by modeRate systemic hypertension, a relatively low afferent to efferent arteriolar resistance Ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in amelioRating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated Rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all Rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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renal disease susceptibility and hypertension are under independent genetic control in the Fawn Hooded Rat
Nature Genetics, 1996Co-Authors: Donna M Brown, A P Provoost, Mark J Daly, Eric S Lander, Howard J JacobAbstract:Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening complications such as end-stage renal disease, coronary artery disease and stroke. Why some patients develop complications is unclear, but only susceptibility genes may be involved. To test this notion, we studied crosses involving the Fawn-Hooded Rat, an animal model of hypertension that develops chronic renal failure. Here, we report the localization of two genes, Rf-1 and Rf-2, responsible for about half of the genetic variation in key indices of renal impairment. In addition, we localize a gene, Bpfh-1, responsible for about 26% of the genetic variation in blood pressure. Rf-1 strongly affects the risk of renal impairment, but has no significant effect on blood pressure. Our results show that susceptibility to a complication of hypertension is under at least partially independent genetic control from susceptibility to hypertension itself.
Richard P E Van Dokkum - One of the best experts on this subject based on the ideXlab platform.
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renal myogenic constriction protects the kidney from age related hypertensive renal damage in the Fawn Hooded Rat
Journal of Hypertension, 2013Co-Authors: Peter Vavrinec, Robert H Henning, Maaike Goris, Sjoerd W Landheer, Hendrik Buikema, Richard P E Van DokkumAbstract:Introduction:Intact myogenic constriction plays a role in renal blood flow autoregulation and protection against pressure-related (renal) injury. However, to what extent alteRations in renal artery myogenic constriction are involved in development of renal damage during aging is unknown. Therefore, we studied two strains of Fawn-Hooded Rats, which differ in expression of hypertension and chronic renal failure.Methods:Ten-week-old Fawn-Hooded hypertensive (FHH) and Fawn-Hooded low blood pressure (FHL) Rats were followed for SBP and proteinuria for 1 year. At 52 weeks of age, the kidney was removed and studied for focal glomerulosclerosis (FGS) and glomerular cross-sectional area, and myogenic constriction of isolated small renal arteries in a vessel perfusion set up. Renal myogenic constriction and FGS were additionally determined in 10-week-old Fawn-Hooded Rats.Results:At young age, Fawn-Hooded Rats did not differ in SBP, FGS, and urinary protein excretion, but renal artery myogenic constriction already was significantly smaller (approximate to 50%) in FHH compared with FHL Rats. Aging in Fawn-Hooded Rats was associated with increase in SBP and urinary protein excretion and loss of renal artery myogenic constriction. These changes occurred in both Fawn-Hooded strains, although that in FHH Rats the onset of hypertension occurred earlier and the increase in proteinuria by far exceeded (>4 times) that observed in FHL Rats, and came along with 5.5 times increase in FGS and 1.3 times increase in glomerular cross-sectional area and significantly less preserved renal artery myogenic constriction in FHH Rats.Conclusion:Better preservation of renal myogenic constriction protects the kidney from age-related hypertensive renal damage in the Fawn-Hooded Rat.
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renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn Hooded Rat
American Journal of Physiology-renal Physiology, 2010Co-Authors: Peter Ochodnický, A P Provoost, Robert H Henning, Hendrik Buikema, Dick De Zeeuw, Richard P E Van DokkumAbstract:It is unknown whether generalized vascular dysfunction precedes the development of kidney disease. Therefore, we studied myogenic constriction and endothelium-mediated dilatory responses in two inb...
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altered renal hemodynamics and impaired myogenic responses in the Fawn Hooded Rat
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1999Co-Authors: Richard P E Van Dokkum, A P Provoost, Howard J Jacob, Chengwen Sun, Richard J RomanAbstract:The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contribu...
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Impaired autoregulation of renal blood flow in the Fawn-Hooded Rat
The American journal of physiology, 1999Co-Authors: Richard P E Van Dokkum, Abraham P. Provoost, Magdalena Alonso-galicia, Howard J JacobAbstract:The responses to changes in renal perfusion pressure (RPP) were compared in 12-wk-old Fawn-Hooded hypertensive (FHH), Fawn-Hooded low blood pressure (FHL), and August Copenhagen Irish (ACI) Rats to...
David H Overstreet - One of the best experts on this subject based on the ideXlab platform.
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antidepressant like effects of nicotine and reduced nicotinic receptor binding in the Fawn Hooded Rat an animal model of co morbid depression and alcoholism
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2009Co-Authors: Yousef Tizabi, Amir H Rezvani, Bruk Getachew, Sheketha R Hauser, David H OverstreetAbstract:A strong positive association between depression and alcoholism is evident in epidemiological studies. Curiously, the incidence of smoking (nicotine intake) is also very high among depressed individuals. Because neuronal nicotinic receptors have been implicated in mood regulation as well as in reinforcing effects of alcohol, it was of interest to determine whether inherent changes in these receptors may be manifested in an animal model that expresses both depressive-like characteristics and high alcohol intake. Thus, Fawn-Hooded (FH) Rats along with their control ACI Rats were used to measure the density of the high affinity nicotinic receptor in discrete brain regions. Furthermore, the effects of acute and chronic nicotine on depressive-like characteristics of FH Rats were also evaluated. Measurements of [3H]cytisine binding (selective for α4β2 nicotinic receptor subtype) revealed a reduction in these receptors only in the striatum of FH Rats, a result very similar to that observed in selectively-bred alcohol-preferring (P) Rats. AdministRation of nicotine acutely (0.4 mg/kg, sc) resulted in a significant reduction of immobility in the forced swim test (FST) in FH Rats only, implying an antidepressant-like effect of nicotine. Another group of FH Rats were administered 0.4 mg/kg nicotine (daily, sc) for 14 days and their behavior in the FST was evaluated 22–24 h after the last injection. In this case, nicotine also had a significant antidepressant-like effect in FH Rats suggesting no tolerance to nicotine had occurred. The effects of nicotine on FST behavior are very similar to those observed in Flinders Sensitive Line Rats, a putative animal model of depression. Together, these findings provide additional evidence for antidepressant-like effects of nicotine and strengthen the postulated association between striatal nicotinic receptors and high alcohol intake. Thus, nicotinic receptors could be suitable targets for the development of novel pharmacotherapy for treatment of depression and possibly alcoholism.
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further genetic characterization of the Fawn Hooded fh wjd Rat an animal model of comorbid depression and alcoholism
Psychiatric Genetics, 2007Co-Authors: Amir H Rezvani, David H Overstreet, Mario A Cleves, Abbas ParsianAbstract:Objective The main objective of this study was a more detailed genetic characterization of the alcohol preferring Fawn-Hooded Rat and its intercrosses. Fawn-Hooded Rats drink substantially more alcohol voluntarily than the ACI Rats. The Fawn-Hooded Rats were shown to be more immobile in the forced-swimming test and to drink more saccharin. Recent comparisons of the parental strains with F1 and F2 intercrosses revealed that the alcohol and saccharin intakes were positively correlated with each other but not with immobility. Methods The F1 and F2 progeny were geneRated by intercrossing the Fawn-Hooded and ACI/N Rats. Data from the F2 progeny, their F1 parents and progenitors were used to estimate heritability. Results Heritability was estimated for alcohol intake (75.6% in males and 67.1% in females), alcohol preference (64.7% in males and 39.2% in females), saccharin intake (50.8% in males and 37.5% in females), and immobility (50.2% in males and 72.1% in females). This same data provided estimates of the number of genes involved in these phenotypes between three and six. We also took advantage of the fact that both progenitor strains are pigmented, so a tremendous variety of coat colors were present in the F2 progeny (i.e. black, black-Hooded, agouti, agouti-Hooded, Fawn, Fawn-Hooded, orange, and orange-Hooded). Coat color analyses indicated that none of the variables significantly varied with coat color. A high correlation however, was observed between alcohol intake and preference in each group. Significant correlations between alcohol and saccharin intakes were seen only in some groups. Conclusion These findings suggest that these phenotypes might be regulated by multiple genes, which could be detected in quantitative trait loci. These analyses are currently underway and will provide a novel approach in understanding the genetics of voluntary alcohol drinking.
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modulation of high alcohol drinking in the inbred Fawn Hooded fh wjd Rat strain implications for treatment
Addiction Biology, 2006Co-Authors: David H Overstreet, Feng Chen, Amir H Rezvani, Michael S Cowen, Andrew J. LawrenceAbstract:The Fawn‐Hooded Rat (FH/Wjd) is an inbred alcohol-preferring Rat strain, unlike most of the other strains that were selectively bred for high alcohol intake and preference. It was chosen for study some 16 years ago because of a reported mutation that disrupted platelet serotonin function. Although the FH/Wjd Rat has high alcohol intake ( > 5 g/kg/day) and preference ( > 65%), interbreeding with an alcohol-non-preferring inbred strain suggested that these measures are unrelated to the serotonin abnormality. Similarly, the exaggeRated immobility of the FH/Wjd Rats in the forced swim test did not correlate with the high alcohol intake. Many compounds have been tested in the FH/Wjd Rats after both acute and chronic treatment and a substantial number of them have proved effective. However, as the case with opiate antagonists, tolerance to the effects of the drug can develop. An up-regulation of opioid receptors accompanied the chronic treatment and this mechanism may account for the development of tolerance. Tolerance to opiate antagonists has also been demonstRated in two of the selectively bred alcohol-preferring Rat lines, but it is unknown whether this process may contribute to the relapses seen in individuals being treated with naltrexone. Other drugs that reliably decrease alcohol intake in the FH/Wjd Rats include the 5-hydroxytryptamine-2A receptor antagonist, amperozide, the mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and herbal derivatives such as ibogaine, St. John’s wort and kudzu extract. Thus, studies in the FH/Wjd Rat have led to the discovery of a wide variety of targets for the development of novel agents to treat alcoholism. The fact that several of these drugs were shown to reduce alcohol intake in some of the selectively bred alcohol-preferring Rat lines and/or alcohol-preferring vervet monkeys increases our confidence that they are good candidates for further development.
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reduced 5 ht3 receptor binding and lower baseline plus maze anxiety in the alcohol preferring inbred Fawn Hooded Rat
Pharmacology Biochemistry and Behavior, 2004Co-Authors: Julie G Hensler, Clyde W Hodge, David H OverstreetAbstract:Abstract The present investigation sought to explore the relationship between the 5-HT 3 receptor and anxiety-like behavior in Fawn-Hooded (FH/Wjd) Rats, an inbred strain that exhibits a high intake and preference for ethanol, and the alcohol-nonpreferring ACI/N strain. Using quantitative autoradiography, we examined whether there were differences in central 5-HT 3 receptor binding in FH/Wjd versus ACI/N Rats. Ten to 14 days prior to being used in the autoradiographic studies, Rats were first confirmed to be representative of their strains by subjecting them to a two-bottle choice procedure for 2 weeks. The binding of [ 3 H]LY 278584 to 5-HT 3 receptors was significantly reduced in frontal cortex, CA1 region of hippocampus, and in the medial and lateral nuclei of the amygdala of FH/Wjd versus ACI/N Rats. In the anterior cingulate cortex and in the dentate gyrus region of the hippocampus the reduction in [ 3 H]LY 278548 binding in the FH/Wjd versus ACI/N strain (40% and 41%, respectively) did not reach statistical significance. In a sepaRate group of animals, the effects of the 5-HT 3 receptor antagonist MDL 72222 (3 mg/kg ip) on anxiety-related behaviors were assessed in the elevated plus maze. In vehicle-treated Rats, the FH/Wjd strain exhibited significantly greater percent of time spent on the open arms and percent open arm entries, an indication of less anxiety. Pretreatment with MDL 72222 did not alter these behaviors in the FH/Wjd Rats, but had an anxiolytic-like effect in the ACI/N strain, significantly increasing the percent of time spent on the open arms and percent open arm entries. Further research into 5-HT 3 receptor function in the alcohol-preferring FH/Wjd Rats is needed to elucidate the relationship among 5-HT 3 receptors, alcohol drinking, and anxiety.
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behavioral differences between two inbred strains of Fawn Hooded Rat a model of serotonin dysfunction
Psychopharmacology, 1996Co-Authors: David H Overstreet, Amir H RezvaniAbstract:The Fawn-Hooded Rat (FH) strain has attracted the attention of some psychopharmacologists because of reports of its exaggeRated immobility in the swim test, hypercortisolemia, excessive voluntary intake of alcohol, platelet and central serotonin abnormalities and subsensitivity to serotonergic agonists. However, there appears to be some controversy over several behavioral and physiological characteristics of these Rats. The present paper proposes that the lack of reproducible findings can be traced to there being several distinct inbred strains of FH Rats. Of the two compared in this communication, the FH/Wjd strain is more immobile in the forced swim test, spends more time in the open arms of the elevated plus maze, and drinks more saccharin and alcohol voluntarily than the FH/Har (Iowa Reactive) strain. Future workers are cautioned to report the source of their FH Rats.
Timothy W Higenbottam - One of the best experts on this subject based on the ideXlab platform.
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The Pulmonary Hypertensive Fawn-Hooded Rat Has a Normal Serotonin Transporter Coding Sequence
2013Co-Authors: Anamaria Gonzalez, Adrian P L Smith, Celia J. Emery, Timothy W HigenbottamAbstract:The coding sequence of the serotonin transporter gene was compared in two strains of Rat—the Wistar and the Fawn-Hooded Rat (FHR). The FHR has an inherited platelet storage-pool deficiency and a widespread impairment of serotonin storage. It is also susceptible to systemic and pulmonary hypertension. The FHR provides a model to study the genetics in human systemic and pulmonary hypertension. We measured platelet function in these two strains by measuring incorpoRation of radiolabeled serotonin into a platelet suspension and found significant differences in serotonin uptake and release. The coding sequence for the serotonin transporter in the FHR has yet to be reported. No differences were found in the predicted amino acid sequence between these two strains of Rat, either in the platelet or the lung samples or when compared with the published sequence of the brown Rat. We conclude that differences in the primary structure of the serotonin transporter gene do not account for the altered serotonin storage in the FHR strain. Gonzalez
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the pulmonary hypertensive Fawn Hooded Rat has a normal serotonin transporter coding sequence
American Journal of Respiratory Cell and Molecular Biology, 1998Co-Authors: Anamaria Gonzalez, Adrian P L Smith, Celia Emery, Timothy W HigenbottamAbstract:The coding sequence of the serotonin transporter gene was compared in two strains of Rat-the Wistar and the Fawn-Hooded Rat (FHR). The FHR has an inherited platelet storage-pool deficiency and a widespread impairment of serotonin storage. It is also susceptible to systemic and pulmonary hypertension. The FHR provides a model to study the genetics in human systemic and pulmonary hypertension. We measured platelet function in these two strains by measuring incorpoRation of radiolabeled serotonin into a platelet suspension and found significant differences in serotonin uptake and release. The coding sequence for the serotonin transporter in the FHR has yet to be reported. No differences were found in the predicted amino acid sequence between these two strains of Rat, either in the platelet or the lung samples or when compared with the published sequence of the brown Rat. We conclude that differences in the primary structure of the serotonin transporter gene do not account for the altered serotonin storage in the FHR strain.
