Molecular basis of parental contributions to the behavioural tolerance of elevated pCO 2 in a coral reef fish

Knowledge of adaptive potential is crucial to predicting the impacts of ocean acidification (OA) on marine organisms. In the spiny damselfish, Acanthochromis polyacanthus , individual variation in behavioural tolerance to elevated pCO 2 has been observed and is associated with offspring gene expression patterns in the brain. However, the maternal and paternal contributions of this variation are unknown. To investigate parental influence of behavioural pCO 2 tolerance, we crossed pCO 2 -tolerant fathers with pCO 2 -sensitive mothers and vice versa, reared their offspring at control and elevated pCO 2 levels, and compared the juveniles' brain transcriptional programme. We identified a large influence of parental phenotype on expression patterns of offspring, irrespective of environmental conditions. Circadian rhythm genes, associated with a tolerant parental phenotype, were uniquely expressed in tolerant mother offspring, while tolerant fathers had a greater role in expression of genes associated with histone binding. Expression changes in genes associated with neural plasticity were identified in both offspring types: the maternal line had a greater effect on genes related to neuron growth while paternal influence impacted the expression of synaptic development genes. Our results confirm cellular mechanisms involved in responses to varying lengths of OA exposure, while highlighting the parental phenotype's influence on offspring molecular phenotype.

Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure

<p>Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three main objectives. 1. To develop a behavioural assay to examine the effects of acute and repeated MDMA exposure. 2. To use this behavioural assay to determine whether functional changes in serotonin (5-HT)2a or 5-HT2c receptors accompany tolerance to the effects of MDMA. 3. To attempt to reverse behavioural tolerance and 5-HT deficits by administering a treatment that has been shown to desensitise the 5-HT1a autoreceptor. Methods: In separate groups of rats the dose effect curves for MDMAproduced hyperactivity were determined (0.0, 1.0, 3.3, 10.0 mg/kg). In additional groups the effect of MDMA pretreatment (4 X 10mg/kg MDMA injections at 2 hour intervals) or saline vehicle on MDMA-produced hyperactivity was assessed. To determine the experimental parameters for MDMA effects in the Emergence Test (ET) separate groups of rats received MDMA (0.0, 3.3 mg/kg) and were either habituated to a hide box for various periods (15, 30, 45mins) or exposed to the test arena 3 times over a period of days (day 1, 5, 9) or injected daily in the home cage with MDMA (0.0, 3.3mg/kg) for 3 days. Emergence latency following injections of MDMA (0.0, 3.3mg/kg), the 5-HT2a /c agonistm-CPP (0.0, 0.3, 0.6 or 1.25 m/kg), the 5-HT releasing stimulant, fenfluramine (0.0, 1.0, 2.0 mg/kg), and the 5-HT2a agonist DOI (0.0, 1.0, 2.0 mg/kg) was measured. The role of 5-HT2c receptors was assessed by determining the effect of the 5-HT2c antagonist, RS102221 (0.0, 0.25, 0.5, 1.0 mg/kg). The effect of MDMA pretreatment on MDMA (0.0, 3.3 mg/kg), m-CPP (1.25 mg/kg), or fenfluramine (2.0mg/kg) induced increases in emergence latency was also assessed. The functional status of the 5-HT1a autoreceptor following MDMA pretreatment was determined by measuring the effect of the 5-HT1a agonist, 8- OHDPAT (0.0, 0.315, 0.0625, 0.125, 0.25, 0.5 mg/kg, SC), on body temperature. The ability of the 5-HT1a antagonist, WAY100635 (0.0, 0.01, 0.1, 1.0mg/kg, SC, 1 X daily for 7 days or by local injection of 0.0 or 500 ng into the dorsal raphe) to reverse the attenuation of MDMA-induced hyperactivity following MDMA pretreatment was examined. Effects of various treatments on tissue levels of 5-HT and 5-HIAA were also measured using HPLC with EC. Results: MDMA produced dose-dependent hyperactivity and tolerance was produced by MDMA pretreatment. MDMA (3.3mg/kg) increased emergence latency following a 30 minute habituation period and this effect was reduced in MDMA-pretreated rats. Fenfluramine and m-CPP but not DOI also increased emergence latency in a dose-dependent manner. RS102221 dose dependently blocked the acute effects of MDMA and m-CPP. Two weeks following MDMA pretreatment rats were tolerant to the effects of MDMA and fenfluramine, but not m-CPP. MDMA pretreatment also produced significant reductions in tissue levels of 5-HT and 5-HIAA. Subcutaneous WAY100635 administration failed to reverse the behavioural and neurochemical deficits produced by MDMA pretreatment but local administration increased MDMA-produced hyperactivity in saline and MDMA pretreated rats and reversed MDMA-produced 5-HT tissue depletions. Conclusion: The Emergence Test is a behavioural assay sensitive to the effects of acute and repeated MDMA exposure. Following MDMA pretreatment behavioural tolerance as measured by the ET is likely to be due to impaired 5-HT release rather than changes in 5-HT2a or 5-HT2c receptor responses. Because partial reversal of tolerance and 5-HT deficits following repeated MDMA administration was achieved through local DRN 5-HT1a antagonist administration the 5-HT1a autoreceptor may prove to be a clinical target for the reversal of MDMA produced deficits.</p>

Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure

<p>Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three main objectives. 1. To develop a behavioural assay to examine the effects of acute and repeated MDMA exposure. 2. To use this behavioural assay to determine whether functional changes in serotonin (5-HT)2a or 5-HT2c receptors accompany tolerance to the effects of MDMA. 3. To attempt to reverse behavioural tolerance and 5-HT deficits by administering a treatment that has been shown to desensitise the 5-HT1a autoreceptor. Methods: In separate groups of rats the dose effect curves for MDMAproduced hyperactivity were determined (0.0, 1.0, 3.3, 10.0 mg/kg). In additional groups the effect of MDMA pretreatment (4 X 10mg/kg MDMA injections at 2 hour intervals) or saline vehicle on MDMA-produced hyperactivity was assessed. To determine the experimental parameters for MDMA effects in the Emergence Test (ET) separate groups of rats received MDMA (0.0, 3.3 mg/kg) and were either habituated to a hide box for various periods (15, 30, 45mins) or exposed to the test arena 3 times over a period of days (day 1, 5, 9) or injected daily in the home cage with MDMA (0.0, 3.3mg/kg) for 3 days. Emergence latency following injections of MDMA (0.0, 3.3mg/kg), the 5-HT2a /c agonistm-CPP (0.0, 0.3, 0.6 or 1.25 m/kg), the 5-HT releasing stimulant, fenfluramine (0.0, 1.0, 2.0 mg/kg), and the 5-HT2a agonist DOI (0.0, 1.0, 2.0 mg/kg) was measured. The role of 5-HT2c receptors was assessed by determining the effect of the 5-HT2c antagonist, RS102221 (0.0, 0.25, 0.5, 1.0 mg/kg). The effect of MDMA pretreatment on MDMA (0.0, 3.3 mg/kg), m-CPP (1.25 mg/kg), or fenfluramine (2.0mg/kg) induced increases in emergence latency was also assessed. The functional status of the 5-HT1a autoreceptor following MDMA pretreatment was determined by measuring the effect of the 5-HT1a agonist, 8- OHDPAT (0.0, 0.315, 0.0625, 0.125, 0.25, 0.5 mg/kg, SC), on body temperature. The ability of the 5-HT1a antagonist, WAY100635 (0.0, 0.01, 0.1, 1.0mg/kg, SC, 1 X daily for 7 days or by local injection of 0.0 or 500 ng into the dorsal raphe) to reverse the attenuation of MDMA-induced hyperactivity following MDMA pretreatment was examined. Effects of various treatments on tissue levels of 5-HT and 5-HIAA were also measured using HPLC with EC. Results: MDMA produced dose-dependent hyperactivity and tolerance was produced by MDMA pretreatment. MDMA (3.3mg/kg) increased emergence latency following a 30 minute habituation period and this effect was reduced in MDMA-pretreated rats. Fenfluramine and m-CPP but not DOI also increased emergence latency in a dose-dependent manner. RS102221 dose dependently blocked the acute effects of MDMA and m-CPP. Two weeks following MDMA pretreatment rats were tolerant to the effects of MDMA and fenfluramine, but not m-CPP. MDMA pretreatment also produced significant reductions in tissue levels of 5-HT and 5-HIAA. Subcutaneous WAY100635 administration failed to reverse the behavioural and neurochemical deficits produced by MDMA pretreatment but local administration increased MDMA-produced hyperactivity in saline and MDMA pretreated rats and reversed MDMA-produced 5-HT tissue depletions. Conclusion: The Emergence Test is a behavioural assay sensitive to the effects of acute and repeated MDMA exposure. Following MDMA pretreatment behavioural tolerance as measured by the ET is likely to be due to impaired 5-HT release rather than changes in 5-HT2a or 5-HT2c receptor responses. Because partial reversal of tolerance and 5-HT deficits following repeated MDMA administration was achieved through local DRN 5-HT1a antagonist administration the 5-HT1a autoreceptor may prove to be a clinical target for the reversal of MDMA produced deficits.</p>

Disease tolerance alters host competence in a wild songbird

Individuals can express a range of disease phenotypes during infection, with important implications for epidemics. Tolerance, in particular, is a host response that minimizes the per-pathogen fitness costs of infection. Because tolerant hosts show milder clinical signs and higher survival, despite similar pathogen burdens, their potential for prolonged pathogen shedding may facilitate the spread of pathogens. To test this, we simulated outbreaks of mycoplasmal conjunctivitis in house finches, asking how the speed of transmission varied with tissue-specific and behavioural components of tolerance, milder conjunctivitis and anorexia for a given pathogen load, respectively. Because tissue-specific tolerance hinders pathogen deposition onto bird feeders, important transmission hubs, we predicted it would slow transmission. Because behavioural tolerance should increase interactions with bird feeders, we predicted it would speed transmission. Our findings supported these predictions, suggesting that variation in tolerance could help identify individuals most likely to transmit pathogens.

Foraging behaviour of the epaulette shark Hemiscyllium ocellatum is not affected by elevated CO2

Increased oceanic uptake of atmospheric carbon dioxide (CO2) is a threat to marine organisms and ecosystems. Among the most dramatic consequences predicted to date are behavioural impairments in marine fish which appear to be caused by the interference of elevated CO2 with a key neurotransmitter receptor in the brain. In this study, we tested the effects of elevated CO2 on the foraging and shelter-seeking behaviours of the reef-dwelling epaulette shark, Hemiscyllium ocellatum. Juvenile sharks were exposed for 30 d to control CO2 (400 µatm) and two elevated CO2 treatments (615 and 910 µatm), consistent with medium- and high-end projections for ocean pCO2 by 2100. Contrary to the effects observed in teleosts and in some other sharks, behaviour of the epaulette shark was unaffected by elevated CO2. A potential explanation is the remarkable adaptation of H. ocellatum to low environmental oxygen conditions (hypoxia) and diel fluctuations in CO2 encountered in their shallow reef habitat. This ability translates into behavioural tolerance of near-future ocean acidification, suggesting that behavioural tolerance and subsequent adaptation to projected future CO2 levels might be possible in some other fish, if adaptation can keep pace with the rate of rising CO2 levels.