Potential serotonin 5-HT1A and dopamine D4 receptor modulation of the discriminative stimulus effects of amphetamine in rats

Marona‐Lewicka, Danuta; Nichols, David E.

doi:10.1097/fbp.0b013e328349fc31

Cited by 10 publications

(3 citation statements)

References 49 publications

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“…Like many drugs WAY is selective but not specific for certain receptors. At high doses WAY antagonizes dopamine-4 (D4) receptors [25], however the concentration we used how is below that shown to block D4 receptors in vivo [25]…”

Section: Experimental Protocolsmentioning

confidence: 99%

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA

Zaretsky¹,

Zaretskaia²,

DiMicco³

et al. 2013

Neuroscience Letters

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Acute and chronic complications from the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) are linked to activation of the hypothalamic-pituitary-adrenal (HPA) axis. How MDMA activates the HPA axis is not known. HPA responses to stress are known to be mediated through the paraventricular (PVH) hypothalamus and to involve serotonin-1a (5-HT1A) receptors. We sought to determine if the PVH and 5-HT1A receptors were also involved in mediating HPA responses to MDMA. Rats were pretreated with either saline or a 5-HT1A antagonist, WAY-100635 (WAY), followed by a systemic dose of MDMA (7.5 mg/kg i.v.). Animals pretreated with WAY had significantly lower plasma ACTH concentrations after MDMA. To determine if neurons in the PVH were involved, and if their involvement was mediated by 5-HT1A receptors, rats implanted with guide cannulas targeting the PVH were microinjected with the GABAA receptor agonist muscimol, aCSF, or WAY followed by MDMA. Compared to aCSF microinjections of muscimol significantly attenuated the MDMA-induced rise in plasma ACTH (126 vs. 588 pg/ml, P=<0.01). WAY had no effect. Our data demonstrates that neurons in the PVH, independent of 5-HT1A receptors, mediate ACTH responses to MDMA.

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Section: Experimental Protocolsmentioning

confidence: 99%

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA

Zaretsky¹,

Zaretskaia²,

DiMicco³

et al. 2013

Neuroscience Letters

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“…Although LSD has high affinity for a variety of G protein coupled receptors, the potent psychoactive effects of LSD can be attributed to its partial agonist activity at the brain serotonin 5-HT 2A receptor . In behavioral studies in rats, however, there is a time-dependent change in pharmacology, from initial 5-HT 2A receptor activation to dopamine D2-like pharmacology at later times. − …”

Section: Pharmacology Medicinal Chemistry and Structure–activity Rela...mentioning

confidence: 99%

Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

Nichols

2018

ACS Chem. Neurosci.

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Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists insight into the mental processes in their patients. The finding of serotonin in the mammalian brain in 1953, and its structural resemblance to LSD, quickly led to ideas that serotonin in the brain might be involved in mental disorders, initiating rapid research interest in the neurochemistry of serotonin. LSD proved to be physiologically very safe and nonaddictive, with a very low incidence of adverse events when used in controlled experiments. Widely hailed by psychiatry as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended by about 1970, when it was formally placed into Schedule 1 of the Controlled Substances Act of 1970 following its growing popularity as a recreational drug. Within the past 5 years, clinical research with LSD has begun in Europe, but there has been none in the United States. LSD is proving to be a powerful tool to help understand brain dynamics when combined with modern brain imaging methods. It remains to be seen whether therapeutic value for LSD can be confirmed in controlled clinical trials, but promising results have been obtained in small pilot trials of depression, anxiety, and addictions using psilocybin, a related psychedelic molecule.

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“…For this reason, pindolol was added to 8-OH-DPAT. WAY-100,635 has also been a standard drug used in studying the function of the 5-HT 1A receptor, but it was discovered that it also is a potent 168 D 4 agonist [58], and the behavioral effects of WAY-100,635 as a D 4 agonist have not been well 169 defined [but see 59,60]. Systemic injection is perhaps not ideal for studying the manipulation of 170 5-HT receptors, given that the 5-HT receptors, including 5-HT 1A , are widespread and it is possible that the drugs have unintended effects beyond the central nervous system.…”

Section: Drug Protocolmentioning

confidence: 99%

Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running

Claghorn

Fonseca

Thompson

et al. 2016

Physiology & Behavior

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Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (P<0.0001) in a dose-dependent manner, with no dose by linetype interaction. Wheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally.

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Potential serotonin 5-HT1A and dopamine D4 receptor modulation of the discriminative stimulus effects of amphetamine in rats

Cited by 10 publications

References 49 publications

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA

Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running

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