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Aldo Bolten Lucion – 1st expert on this subject based on the ideXlab platform
8 oh dpat in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female ratsNeuroscience & Biobehavioral Reviews, 1998Co-Authors: Rosa Maria Martins De Almeida, Marcia Giovenardi, Helenice Charchat, Aldo Bolten LucionAbstract:
Abstract The experiment evaluated the effects of 8-OH-DPAT on the activity of virgin female rats (diestrus) in the elevated plus maze. The 5-HT1A receptor agonist was infused into the median raphe nucleus (N=60) and medial septal area (N=68) 10 min before the test. Five groups for each brain area were analyzed: intact, saline (0.2 μl) and 8-OH-DPAT (0.2; 0.5 and 2.0 μg rat−1). The following measures were recorded: number of entries onto open and enclosed arms and time spent on the open and enclosed arms. In addition, the frequency of stretch–attend and head-dipping were also evaluated. The results showed that in the median raphe nucleus only the highest dose of 8-OH-DPAT (2.0 μg) increased the percentage of time spent on the open arms. On the other hand, in medial septal area 8-OH-DPAT in the dose of 0.5 μg decreased the percentage of time spent on the open arms, while the doses of 0.2 and 2.0 μg had no significant impact on anxiety. Data suggest that 8-OH-DPAT acting on 5-HT1A somatodendritic autoreceptors decreases anxiety. However, at a specific dosage and acting on postsynaptic receptors of the medial septal area, 8-OH-DPAT can increase anxiety.
8 oh dpat in the median raphe dorsal periaqueductal gray and corticomedial amygdala nucleus decreases but in the medial septal area it can increase maternal aggressive behavior in ratsPsychopharmacology, 1997Co-Authors: Rosa Maria Martins De Almeida, Aldo Bolten LucionAbstract:
The purpose of the present study was to analyze the role of somatodendritic autoreceptors and postsynaptic 5-HT1A receptors in the modulation of maternal aggressive behavior. The 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was microinjected (0.2, 0.5 and 2.0 μg/0.2 μl) in different brain areas of female Wistar rats: median raphe nucleus (MnR); medial septal area (MS); anterior corticomedial amygdaloid nucleus (ACoM); and dorsal periaqueductal gray (DPAG). The behaviors of lactating female rats with pups against a conspecific male intruder were recorded on day 7 post-partum. Results showed that in the median raphe nuclei, in the dorsal periaqueductal gray and in the corticomedial amygdaloid nucleus 8-OH-DPAT decreased maternal aggression; while in the medial septum, the intermediate dose (0.5 μg/0.2 μl) of the 5-HT1A receptor agonist increased the aggressive behavior of the lactating female rat. It is concluded that the main role of the 5-HT1A somatodendritic autoreceptors and the postsynaptic receptors of the brain areas studied is to decrease maternal aggression, however, at a specific dosage, 8-OH-DPAT acting on postsynaptic receptors of the medial septal area can increase aggressiveness.
Paul J Fletcher – 2nd expert on this subject based on the ideXlab platform
Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulationPharmacology Biochemistry and Behavior, 1995Co-Authors: Paul J Fletcher, Maria Tampakeras, John S. YeomansAbstract:
The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reduces the activity of brain 5-HT neurons via somatodendritic autoreceptors located in the midbrain raphe nuclei. This action of 8-OH-DPAT results in reduced 5-HT synthesis and release of 5-HT in terminal regions. Previous studies have shown that injecting 8-OH-DPAT into the raphe nuclei stimulates feeding, sexual behaviour, and locomotor activity, and serves as an unconditioned stimulus for inducing a conditioned place preference. This behavioural profile suggests that raphe injections of 8-OH-DPAT facilitate reward-related behaviour. The present study tested this hypothesis by investigating the effects of median raphe injections of 8-OH-DPAT on sensitivity to lateral hypothalamic (LH) self-stimulation. Frequencies required to sustain half-maximal rates of responding were determined following injection of saline or various doses of 8-OH-DPAT (0.2–5 μg) into the median raphe. In four rats with accurate injection sites 8-OH-DPAT dose-dependently lowered frequency thresholds by up to 40%. In the remaining rats injection sites were located outside the median raphe, and 8-OH-DPAT either slightly raised or failed to lower frequency thresholds. These results show that 8-OH-DPAT injected into the median raphe facilitates brain stimulation reward, and suggest that acute reductions in 5-HT neurotransmission may enhance sensitivity to rewarding stimuli. The possible interactions between 5-HT neurons and efferent systems utilizing dopamine and acetylcholine as neurotransmitters in mediating this effect are discussed.
conditioned place preference induced by microinjection of 8 oh dpat into the dorsal or median raphe nucleusPsychopharmacology, 1993Co-Authors: Paul J Fletcher, Zhihui Ming, Guy A HigginsAbstract:
Experiments were conducted to examine the ability of the selective 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to induce a conditioned place preference following peripheral injection, and direct microinjection into the dorsal or median raphe nuclei. An unbiased place preference paradigm was used in which control animals showed no preference for either of two compartments differing in terms of colour (white versus black), floor texture (rough versus smooth) and olfactory cues (no odour versus acetic acid odour). Drug treatments were paired with access to either of the two compartments, and saline injections were paired with access to the other compartment. Rats experiencing a low dose of 8-OH-DPAT (125 µg/kg) with a specific compartment demonstrated a significant preference for that compartment over one paired with saline injections. The magnitude of this effect was similar to that observed in rats treated with 1.5 mg/kgd-amphetamine. A significant place preference was found in animals receiving injections of 8-OH-DPAT in the dorsal raphe at 0.1 µg but not 1 µg. Animals also displayed a preference for the compartment paired with 1 µg 8-OH-DPAT injected into the median raphe; lower doses were not effective. These results indicate that the mechanism by which 8-OH-DPAT induces a conditioned place preference involves activation of raphe somatodendritic 5-HT1A autoreceptors, leading to a reduction in 5-HT neurotransmission. This demonstration of the rewarding properties of 8-OH-DPAT, together with previous results showing increased feeding and sexual behaviour following 8-OH-DPAT treatment, strongly suggests an important role for brain 5-HT systems in reward and reinforcement processes.
Opiate antagonists inhibit feeding induced by 8-OH-DPAT: possible mediation in the nucleus accumbens.Brain Research, 1991Co-Authors: Paul J FletcherAbstract:
Previous work has shown that the 5-hydroxytryptamine (5-HT)1A receptor agonist8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits a variety of behaviours, including feeding in rats. These effects are accompanied by reduced 5-HT neurotransmission resulting from activation of somatodendritic 5-HT receptors located in the midbrain raphe nuclei. Dopamine antagonists injected either peripherally or into the nucleus accumbens reverse 8-OH-DPAT-induced feeding. Thus a facilitation of dopamine activity, secondary to reduced 5-HT activity, may be involved in mediating 8-OH-DPAT-induced feeding. Opiate antagonists have been shown previously to reduce several dopamine-dependent behaviours including feeding induced by dopaminergic drugs, tail pinch and electrical brain stimulation. Therefore experiments were conducted to assess the effects of opiate antagonists on feeding induced by peripheral, and raphe injection of 8-OH-DPAT in free-feeding rats. Following SC injection naloxone (0.1–10 mg/kg) dose-dependently reduced the feeding response induced by 100 μg/kg 8-OH-DPAT (SC). The lowest effective dose of naloxone was 1 mg/kg. This dose of naloxone also suppressed feeding induced by 8-OH-DPAT injected into either the dorsal (1 μg) or median (0.5 μg) raphe. Microinjecting 2 μg naloxone together with 8-OH-DPAT into either of these sites failed to prevent the increased feeding. These results indicate that the effects of naloxone are mediated at sites distal to the raphe nuclei. One possible site may be the nucleus accumbens, since methyl-naltrexone (0.3, 1 or 3 μg) injected into this site blocked the feeding responses to intra-raphe 8-OH-DPAT. Examination of the effects of naloxone and methyl-naltrexone in food-deprived rats ruled out intrinsic anorectic actions of these drugs as an explanation for the antagonism of 8-OH-DPAT-induced feeding. The results may indicate that reduced 5-HT function increases opiate activity in the nucleus accumbens. Alternatively opiate antagonists may prevent the indirect facilitation of dopamine activity resulting from a reduction in 5-HT neurotransmission. Opiate and dopamine systems in the nucleus accumbens play a major role in reward processes. Since opiate and dopamine antagonists reverse 8-OH-DPAT-induced feeding the possible role of reward mechanisms in mediating the effect of 8-OH-DPAT is discussed.
Wouter Koek – 3rd expert on this subject based on the ideXlab platform
[(3)H]-8-OH-DPAT binding in the rat brain raphe area: involvement of 5-HT(1A) and non-5-HT(1A) receptors.British journal of pharmacology, 2000Co-Authors: Marie-bernadette Assié, Wouter KoekAbstract:
1. The 5-HT(1A) agonist 8-OH-DPAT has been shown to have additional 5-HT uptake inhibiting properties. The present work was undertaken to examine further the binding of [(3)H]-8-OH-DPAT in the raphe area of the rat brain, a region rich in 5-HT(1A) receptors and 5-HT uptake sites. 2. 5-HT inhibited [(3)H]-8-OH-DPAT binding in a biphasic manner (pK(i1): 8.82+/-0.01, pK(i2): 6.07+/-0.05, n=4) with the low affinity site representing 36+/-4% of the total population. A biphasic inhibition curve was found also with the 5-HT(1A) antagonist, WAY 100635 (pK(i1): 8.65+/-0.17, pK(i2): 4.26+/-0.38, n=3). In the presence of 1 microM WAY 100635 to mask 5-HT(1A) receptors, 5-HT inhibited [(3)H]-8-OH-DPAT binding in a monophasic manner (pK(i): 6.04+/-0.07, n=3). 3. The affinities of various compounds for sites labelled by [(3)H]-8-OH-DPAT in the presence of 1 microM WAY 100635 and for sites labelled by [(3)H]-citalopram (a selective 5-HT uptake inhibitor) were determined. There was a significant correlation between pK(i) values at 5-HT uptake sites and at non-5HT(1A) sites labelled by [(3)H]-8-OH-DPAT (r=0.80, P
modification of behavioral effects of 8 hydroxy 2 di n propylamino tetralin following chronic ethanol consumption in the rat evidence for the involvement of 5 ht1a receptors in ethanol dependenceEuropean Journal of Pharmacology, 1995Co-Authors: Mark S Kleven, C E Ybema, Michel Hamon, Elisabeth Carilla, Wouter KoekAbstract:
Behavioral effects induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; i.e., lower lip retraction, flat body posture, and forepaw treading) were examined in rats during ethanol withdrawal following a 2-week period of access to a liquid diet containing 9% (v/v) ethanol. After an 18 h withdrawal period, tolerance to 8-OH-DPAT-induced flat body posture and, conversely, sensitization to the effects of 8-OH-DPAT on lower lip retraction were observed in the 9% ethanol group as compared to control rats fed an isocaloric diet. In contrast, 8-OH-DPAT-induced forepaw treading in the 9% ethanol group was not significantly different in comparison to control rats. Plasma corticosterone levels were significantly higher in the ethanol-exposed group than in control animals, an effect which was not additive with the increase in corticosterone levels normally observed after the administration of low doses of 8-OH-DPAT. Altered flat body posture and lower lip retraction responses to a submaximal dose of 8-OH-DPAT (2.5 mg/kg i.p.) were still observed as late as 3 days after withdrawal of the 9% ethanol liquid diet, but were no longer apparent at 7 days. Interestingly, prominent ethanol withdrawal signs such as tremor and rigidity, while occurring on the first day, were completely absent on the third day. Taken together, these results indicate that chronic ethanol exposure differentially alters sensitivity to several pharmacological effects of the 5-HT1A receptor ligand 8-OH-DPAT. They further support the involvement of 5-HT (5-hydroxytryptamine, serotonin) systems in alcohol abuse and therapeutic interventions using 5-HT1A ligands.