Localization of drug reward mechanisms by intracranial injections

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

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d-amphetamine stimulates unconditioned exploration/approach behaviors in crayfish: Towards a conserved evolutionary function of ancestral drug reward

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2011.04.004 ◽

2011 ◽

Vol 99 (1) ◽

pp. 75-80 ◽

Cited By ~ 23

Author(s):

Antonio Alcaro ◽

Jaak Panksepp ◽

Robert Huber

Keyword(s):

Drug Reward ◽

Evolutionary Function ◽

Approach Behaviors

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Effects of Nicotine and Exposure to Cigarette Smoke on Discrete Dopamine and Noradrenaline Nerve Terminal Systems of the Telencephalon and Diencephalon of the Rat: Relationship to Reward Mechanisms and Neuroendocrine Functions and Distribution of Nicotinic Binding Sites in Brain

Tobacco Smoking and Nicotine - Advances in Behavioral Biology ◽

10.1007/978-1-4613-1911-5_15 ◽

1987 ◽

pp. 225-262 ◽

Cited By ~ 7

Author(s):

K. Fuxe ◽

K. Andersson ◽

P. Eneroth ◽

A. Härfstrand ◽

A. Nordberg ◽

...

Keyword(s):

Cigarette Smoke ◽

Nerve Terminal ◽

Binding Sites ◽

Reward Mechanisms ◽

Neuroendocrine Functions

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Digital Social Markets: Exploring the Opportunities and Impacts of Gamification and Reward Mechanisms in Citizen Engagement and Smart City Services

Intelligent Systems, Control and Automation: Science and Engineering - How Smart Is Your City? ◽

10.1007/978-3-030-56926-6_9 ◽

2020 ◽

pp. 103-125

Author(s):

Thomas White ◽

Francesco Marchet

Keyword(s):

Smart City ◽

Citizen Engagement ◽

Reward Mechanisms

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Stress decreases serotonin tone in the nucleus accumbens to promote aversion and potentiate cocaine preference via decreased stimulation of 5-HT1B receptors

10.1101/2021.06.27.450100 ◽

2021 ◽

Author(s):

Harrison M Fontaine ◽

Phillip R Silva ◽

Carlie Neiswanger ◽

Rachelle Tran ◽

Antony D Abraham ◽

...

Keyword(s):

Nucleus Accumbens ◽

Indirect Pathway ◽

Lateral Aspect ◽

Drug Reward ◽

Cholinergic Interneurons ◽

Medial Nucleus ◽

Conditional Deletion ◽

Pharmacological Blockade ◽

Monoaminergic Neurons ◽

Stimulation Of

Stress-induced release of dynorphins (Dyn) activates kappa opioid receptors (KOR) in monoaminergic neurons to produce dysphoria and potentiate drug reward; however, the circuit mechanisms responsible for this effect are not known. We found that conditional deletion of KOR from Slc6a4 (SERT)-expressing neurons blocked stress-induced potentiation of cocaine conditioned place preference (CPP). Within the dorsal raphe nucleus (DRN), two overlapping populations of KOR-expressing neurons: Slc17a8 (VGluT3) and SERT, were distinguished functionally and anatomically. Optogenetic inhibition of these SERT+ neurons potentiated subsequent cocaine CPP, whereas optical inhibition of the VGluT3+ neurons blocked subsequent cocaine CPP. SERT+/VGluT3- expressing neurons were concentrated in the lateral aspect of the DRN. SERT projections from the DRN were observed in the medial nucleus accumbens (mNAc), but VGluT3 projections were not. Optical inhibition of SERT+ neurons produced place aversion, whereas optical stimulation of SERT+ terminals in the mNAc attenuated stress-induced increases in forced swim immobility and subsequent cocaine CPP. KOR neurons projecting to mNAc were confined to the lateral aspect of the DRN, and the principal source of dynorphinergic (Pdyn) afferents in the mNAc was from local neurons. Excision of Pdyn from the mNAc blocked stress-potentiation of cocaine CPP. Prior studies suggested that stress-induced dynorphin release within the mNAc activates KOR to potentiate cocaine preference by a reduction in 5-HT tone. Consistent with this hypothesis, a transient pharmacological blockade of mNAc 5-HT1B receptors potentiated subsequent cocaine CPP. 5-HT1B is known to be expressed on 5-HT terminals in NAc, and 5-HT1B transcript was also detected in Pdyn+, Adora2a+ and ChAT+ (markers for direct pathway, indirect pathway, and cholinergic interneurons, respectively). Following stress exposure, 5-HT1B transcript was selectively elevated in Pdyn+ cells of the mNAc. These findings suggest that Dyn/KOR regulates serotonin activation of 5HT1B receptors within the mNAc and dynamically controls stress response, affect, and drug reward.

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