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Aldo Bolten Lucion - One of the best experts on this subject based on the ideXlab platform.
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8 oh dpat in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female rats
Neuroscience & 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.
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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 rats
Psychopharmacology, 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 - One of the best experts on this subject based on the ideXlab platform.
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Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation
Pharmacology 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.
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conditioned place preference induced by microinjection of 8 oh dpat into the dorsal or median raphe nucleus
Psychopharmacology, 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.
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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.
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Influence of taste and food texture on the feeding responses induced by 8-OH-DPAT and gepirone
Psychopharmacology, 1991Co-Authors: Paul J Fletcher, Martin H. Zack, Donald V. CoscinaAbstract:Previously it has been shown that 5-hydroxytryptamine (5-HT)_1A agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone increase food intake in free-feeding rats. These experiments were conducted to examine the possible influence of taste and textural factors on the feeding responses induced by these two drugs. Separate groups of non-water-deprived rats were given access to one of a variety of different solutions of saccharin (0.02, 0.04, 0.20 and 2.0% w/v) or water for 2 h each day. Rats were then treated with different doses of 8-OH-DPAT (10, 60 or 100 µg/kg) or gepirone (1 or 2.5 mg/kg) in a repeated measures design. Under saline injection an inverted-U shaped concentration-response curve was obtained, with the highest level of intake occurring in rats drinking from the 0.20% saccharin solution. The highest doses of 8-OH-DPAT and gepirone suppressed drinking of saccharin, particularly over the first 30 min of the test period, leading to a flattening of the concentration response curve. At 2 h post-injection 60 µg/kg 8-OH-DPAT enhanced the consumption of the 0.04% saccharin solution only. In a second experiment, 8-OH-DPAT or gepirone was administered to rats eating either standard pelleted chow or the same food presented in powdered form. Both drugs stimulated feeding. However, interactions with food type were found. At 60 and 100 µg/kg 8-OH-DPAT increased eating of both food types equally, but with 500 µg/kg rats are significantly more of the pelleted food. Gepirone at 1 and 2.5 mg/kg also significantly increased pelleted food intake compared to powdered food intake. These results suggest that taste factors alone are unlikely to be a major determinant of 8-OH-DPAT's effects on food intake. On the other hand, food texture may play a significant role in the capacity to elicit feeding after high doses of both 8-OH-DPAT and gepirone.
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dopamine receptor blockade in nucleus accumbens or caudate nucleus differentially affects feeding induced by 8 oh dpat injected into dorsal or median raphe
Brain Research, 1991Co-Authors: Paul J FletcherAbstract:The 5-hydroxytryptamine (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits a variety of behaviours including feeding in rats. These effects are accompanied by a reduction in 5-HT neurotransmission resulting from activation of somatodendritic 5-HT receptors located in the midbrain raphe nuclei. Previous work showing that dopamine receptor antagonists attenuate 8-OH-DPAT-induced feeding indicates that a facilitation of dopamine activity, secondary to reduced 5-HT activity, is involved in the expression of this effect. Microinjection studies were conducted to explore further the nature of this 5-HT-dopamine interaction. Injection of 8-OH-DPAT (0.125–2 μg) into either dorsal or median raphe induced dose-dependent increases in 1 h food intake in non-deprived rats. Pretreatment with haloperidol (0.05 and 0.1 mg/kg s.c.) attenuated the effect induced by median raphe 8-OH-DPAT (0.5 μg) complementing previous results with dorsal raphe 8-OH-DPAT. The feeding resulting from dorsal raphe (1 μg) or median raphe (0.5 μg) 8-OH-DPAT was attenuated by α-flupenthixol (1.25 and 2.5 μg) injected into the nucleus accumbens. α-Flupenthixol in either the dorsolateral or ventrolateral aspects of the caudate nucleus attenuated also the feeding response to dorsal raphe, but not median raphe, 8-OH-DPAT. However, α-flupenthixol in the dorsomedial caudate failed to alter feeding resulting from dorsal raphe 8-OH-DPAT. The results confirm the involvement of dopamine in mediating the effects on feeding of 8-OH-DPAT and suggest that overlapping but different mechanisms are involved in the expression of the feeding resulting from dorsal and median raphe injection of 8-OH-DPAT. Thus, while the nucleus accumbens appears to be involved in both effects, the caudate nucleus is involved only in the effect derived from the dorsal raphe. The nucleus accumbens has been implicated in reward processes, whereas dopamine in the lateral caudate appears to facilitate sensorimotor integration. It is possible that these processes may underlie 8-OH-DPAT feeding. In a broader context these results may have important implications for understanding the diversity of motivated behaviours which can be elicited by 8-OH-DPAT and a reduction in 5-HT function.
Wouter Koek - One of the best experts on this subject based on the ideXlab platform.
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[(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
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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 dependence
European 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.
Rosa Maria Martins De Almeida - One of the best experts on this subject based on the ideXlab platform.
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8 oh dpat in the median raphe nucleus decreases while in the medial septal area it may increase anxiety in female rats
Neuroscience & 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.
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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 rats
Psychopharmacology, 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.
Deborah S. Kreiss - One of the best experts on this subject based on the ideXlab platform.
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chronic administration of the 5 ht1a receptor agonist 8 oh dpat differentially desensitizes 5 ht1a autoreceptors of the dorsal and median raphe nuclei
Synapse, 1997Co-Authors: Deborah S. Kreiss, Irwin LuckiAbstract:The present study investigated alterations of the regulation of serotonin (5-hydroxytryptamine; 5-HT) release by 5-HT1A autoreceptors following single and repeated treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT). Rats were pretreated with 8-OH-DPAT (1.0 mg/kg, s.c.) for 1, 7, or 14 days. The ability of an acute challenge administration of 8-OH-DPAT (1.0 mg/kg, i.p.) to decrease 5-HT release in the ventral striatum and the ventral hippocampus of rats maintained under chloral hydrate anesthesia was examined 24 h after the last pretreatment injection using in vivo microdialysis. The decrease of 5-HT release in the striatum produced by the challenge dose of the 5-HT1A receptor agonist was diminished following 7 and 14 days of pretreatment, but not after 1 day of pretreatment, with 8-OH-DPAT. In contrast, decreases of 5-HT release in the hippocampus by the 8-OH-DPAT challenge were not altered after 1 or 7 days of pretreatment, and only a trend for attenuation appeared after pretreatment for 14 days. The results of the present study indicate that desensitization of 5-HT1A autoreceptors regulating 5-HT release in different brain regions by repeated treatment with 8-OH-DPAT occurs at different rates. Synapse 25:107–116, 1997. © 1997 Wiley-Liss, Inc.
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differential regulation of serotonin 5 ht release in the striatum and hippocampus by 5 ht1a autoreceptors of the dorsal and median raphe nuclei
Journal of Pharmacology and Experimental Therapeutics, 1994Co-Authors: Deborah S. Kreiss, I LuckiAbstract:The present study characterized the pharmacological mechanisms and regional selectivity of the regulation of serotonin (5-HT) release by 5-HT1A autoreceptors. 5-HT release was measured simultaneously in the striatum and ventral hippocampus by using in vivo microdialysis in rats maintained under chloral hydrate anesthesia. Systemic administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produced complete reductions of 5-HT release. The effects of systemic 8-OH-DPAT on 5-HT release were blocked completely by systemic administration of the 5-HT/beta adrenergic receptor antagonist, (-)-propranolol, but not by the beta-1 adrenergic receptor antagonist betaxolol or the beta-2 adrenergic receptor antagonist ICI-118,551. Local administration of 8-OH-DPAT into the striatum or hippocampus through the microdialysis probe did not alter 5-HT release. Local administration of 8-OH-DPAT into the dorsal raphe nucleus reduced 5-HT release in the striatum, but not in the hippocampus. Conversely, administration of 8-OH-DPAT into the median raphe nucleus reduced 5-HT release in the hippocampus, but not in the striatum. The effects of systemic 8-OH-DPAT on striatal 5-HT release were selectively blocked by concurrent administration of (-)-propranolol into the dorsal raphe nucleus, whereas effects of systemic 8-OH-DPAT on hippocampal 5-HT release were selectively blocked by concurrent administration of (-)-propranolol into the median raphe nucleus. The present study suggests that somatodendritic 5-HT1A receptors regulate the release of 5-HT in a regionally dependent manner.
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Desensitization of 5-HT1A autoreceptors by chronic administration of 8-OH-DPAT.
Neuropharmacology, 1992Co-Authors: Deborah S. Kreiss, Irwin LuckiAbstract:The function of 5-HT1A autoreceptors was examined by measuring the ability of the 5-HT1A receptor agonist 8-OH-DPAT to reduce 5-HT release in the striatum using in vivo microdialysis. 8-OH-DPAT reduced the release of 5-HT in the striatum. Chronic treatment with 8-OH-DPAT (1.0 mg/kg s.c.) for 7 days, but not 1 day, attenuated the effect of an acute challenge dose of 8-OH-DPAT. The results of the present study indicate that in vivo microdialysis can be used to study the effects of activation of 5-HT1A autoreceptors on 5-HT release and the regulation of 5-HT release by chronic administration of psychoactive drugs.
