The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior

Carey, Robert J.; DePalma, Gail; Damianopoulos, Ernest N.; Müller, Christian P.; Huston, Joseph P.

doi:10.1007/s00213-004-1917-4

Cited by 72 publications

(33 citation statements)

References 56 publications

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“…First, the retest was given a week after the last drug treatment to prevent any carry-over effects. Second, administration of these drugs at low to moderate doses tends to potentiate locomotor activity when given alone or prior to cocaine (Carey et al, 2002(Carey et al, , 2004Chen and Reith, 1995;De La Garza and Cunningham, 2000;Herges and Taylor, 1998;Müller et al, 2003;Schenk et al, 1991). Lastly, the highest dose of 8-OH-DPAT has been shown to inhibit locomotor activity (Przegalinski and Filip, 1997), but this was true only when it was co-administered with cocaine.…”

Section: Discussionmentioning

confidence: 99%

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

Stanis

Burns

Sherrill

et al. 2008

Drug and Alcohol Dependence

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Heightened impulsivity and differential sensitivity to a drug's behavioral effects are traits that, individually, have been associated with chronic drug use and dependence. Here, we used an animal model to test whether individual differences in cocaine-induced activity are predictive of impulsive choice behavior. Adult, male Sprague-Dawley rats were given cocaine (10 mg/kg, i.p.) and classified into low or high cocaine responders (LCRs and HCRs, respectively) based on their locomotor response in an open-field arena. Rats were then trained in a delay-discounting task that offers a choice between immediately delivered, but smaller reinforcements, or larger reinforcements that are delivered after a delay. We also examined the effects of amphetamine (AMPH; 0.3-1.0 mg/kg) and the 5-HT 1A agonist 8-OH-DPAT (0.3-1.0 mg/kg) on delay discounting. Lastly, all rats were retested in the open-field to determine if phenotypes were stable. We observed baseline differences in choice behavior between the groups, with HCRs behaving more impulsively (i.e., choosing the small reinforcement) compared to LCRs. AMPH decreased choice of the large reinforcement in LCRs, but did not alter choice in HCRs. Impulsive choice was increased in both phenotypes following 8-OH-DPAT, with LCRs exhibiting changes across a wider range of delays. When cocaine-induced openfield behavior was retested, responses in LCRs were similar whereas HCRs showed evidence of tolerance. Our results suggest that differential sensitivity to cocaine-induced locomotion is predictive of impulsivity and the potential neurobiological differences in LCRs and HCRs may provide insight into mechanisms contributing to vulnerability for chronic drug use and/or dependence.

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Section: Discussionmentioning

confidence: 99%

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

Stanis

Burns

Sherrill

et al. 2008

Drug and Alcohol Dependence

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“…Systemic administration of low doses of 8-OHDPAT (0.05 mg/kg) have been reported to preferentially stimulate autoreceptors. Administration of these doses decreased locomotion; these effects were reversed by treatment with the antagonist WAY 100,635 (Carey et al, 2004). Systemic administration of the 5-HT1A receptor antagonist p-MPPF augmented cocaine-induced, but not basal, DA release in the NA (Andrews et al, 2005).…”

Section: Mesolimbic Pathwaymentioning

confidence: 94%

“…5-HT is released somatodendritically and decreases 5-HT cell firing by activating these receptors. At low doses, experimentally employed 5-HT1A agonists such as 8-OHDPAT preferentially stimulate these autoreceptors and thus decrease serotonergic function (Carey et al, 2004). At higher doses, postsynaptic 5-HT1A receptors are also stimulated with a net increase in 5-HT1A-mediated functions.…”

Section: -Ht Receptorsmentioning

confidence: 99%

“…The effects of higher doses of systemically administered 8-OHDPAT may reflect actions on this receptor population. Systemic treatment with moderate doses of 8-OHDPAT increased cocaine-induced locomotion (De La Garza and Cunningham, 2000;Carey et al, 2004). Local infusions of 8-OHDPAT by reverse dialysis into the NA potentiated cocaine-stimulated locomotion but did not affect cocaine-mediated increases in NA 5-HT, arguing that the effects of 8-OHDPAT on postsynaptic receptors were not caused by changes in NA 5-HT release.…”

Section: Mesolimbic Pathwaymentioning

confidence: 99%

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Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…Furthermore, S-15535 suppresses dialysate levels of 5-HT in the hippocampus (Dekeyne et al 2000). It is therefore tempting to speculate that S-15535 and 8-OHDPAT increased cocaine's psychomotor effects by shifting the 5-HT-DA balance to the more dopaminergic side when 5-HT levels decrease (Carey et al 2004(Carey et al , 2005. In SERT −/− models, relatively reduced cocaineinduced 5-HT release (Shen et al 2004) could thus result in a more dopaminergic type of response to cocaine.…”

Section: Enhanced Rewarding Properties Of Cocaine In Sertmentioning

confidence: 99%

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

et al. 2008

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Rationale While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. Objectives To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout (SERT −/− ) rat and the involvement of compensatory changes in 5-HT 1A receptor function are the objectives of the study. Materials and methodsThe SERT −/− rat was tested for cocaine-induced locomotor activity, cocaine-induced conditioned place preference, and intravenous cocaine selfadministration. In addition, the function and expression of 5-HT 1A receptors was assessed using telemetry and autoradiography, respectively, and the effect of 5-HT 1A receptor ligands on cocaine's psychomotor effects were studied.Results Cocaine-induced hyperactivity and conditioned place preference, as well as intravenous cocaine selfadministration were enhanced in SERT −/− rats. Furthermore,

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The 5-HT1A receptor and behavioral stimulation in the rat: effects of 8-OHDPAT on spontaneous and cocaine-induced behavior

Abstract: It is suggested that the facilitatory effect of 8-OHDPAT on cocaine-induced locomotor stimulation is mediated by inhibition of 5-HT(1A) somato-dendritic autoreceptors.

Cited by 72 publications

References 56 publications

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

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