Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats

Porrino, Linda J.; Ritz, Mary C.; Goodman, Nancy L.; Sharpe, Lawrence G.; Kuhar, Michael J.; Goldberg, Steven R.

doi:10.1016/0024-3205(89)90418-9

Cited by 109 publications

(57 citation statements)

References 21 publications

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“…In a mouse model, pretreatment with fluoxetine, a potent inhibitor of the SERT, decreased the latency of cocaine-induced convulsions by 53% and increased the occurrence of seizures in a dose-dependent manner [58]. Similar effects have been reported for other SERT inhibitors [59].…”

Section: Post-receptor Effects Of Cocainesupporting

confidence: 53%

Mechanisms of Acute Cocaine Toxicity

Heard¹,

Palmer²,

Zahniser³

2008

TOPHARMJ

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Abstract:Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporter, neurotransmitter receptor and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine and the effects that these interactions trigger. We also describe the progression of symptoms observed in cocaine poisoning as they relate to serum cocaine concentrations.

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Section: Post-receptor Effects Of Cocainesupporting

confidence: 53%

Mechanisms of Acute Cocaine Toxicity

Heard¹,

Palmer²,

Zahniser³

2008

TOPHARMJ

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“…Fluoxetine, at a dose shown to block reuptake in rats (Wong et al, 1985) and decrease cocaine self-administration (Porrino et al, 1989), failed to block conditioned place aversion to opiate withdrawal. Similarly, the dopamine partial agonist terguride at a dose that blocks cocaine selfadministration (Pulvirenti et al, 1998), methamphetamine self-administration (O Kitamura, GF Koob, L Pulvirenti, unpublished results), and psychostimulant withdrawal (Orsini et al, 2001) failed to block conditioned place aversion to opiate withdrawal.…”

Section: Discussionmentioning

confidence: 93%

“…The doses of terguride, fluoxetine, and acamprosate were chosen because of the effectiveness of these doses in modulating the reinforcing effects of other drugs of abuse. Also, the treatment interval varied between drugs based on their pharmacokinetic differences (see Spanagel et al, 1996aSpanagel et al, , b, 1998Porrino et al, 1989;Cole et al, 2000;Pulvirenti et al, 1998).…”

Section: Experimental Designmentioning

confidence: 99%

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

Stinus

Cador

Zorrilla

et al. 2004

Neuropsychopharmacol

127

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Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 mg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF 1 ) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF 1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

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“…5-HT 3 receptors also appear to play a facilitatory role in the behavioral effects of DA agonists (Layer et al, 1992;Kankaanpaa et al, 1996). Additional studies have failed to find alterations in cocaine-maintained responding resulting from administration of serotonergic drugs (Porrino et al, 1989;Lacosta and Roberts, 1993;Peltier and Schenk, 1993). These seemingly disparate results likely reflect the complexity of interactions between 5-HT and DA systems and the 5-HT receptor subtypes influenced by drug administration.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic Attenuation of the Reinforcing and Neurochemical Effects of Cocaine in Squirrel Monkeys

Czoty¹,

Ginsburg²,

Howell³

2002

J Pharmacol Exp Ther

108

100

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Preclinical studies have documented that serotonin (5-HT) can modulate the behavioral effects of cocaine. The present study examined the ability of 5-HT to attenuate the reinforcing and neurochemical effects of cocaine in nonhuman primates. In squirrel monkeys trained to self-administer cocaine (0.1 and 0.3 mg/injection) under a second-order schedule of i.v. drug delivery, the 5-HT uptake inhibitor alaproclate (3.0 and 10.0 mg/kg) and the 5-HT direct agonist quipazine (0.3-1.0 mg/kg) decreased response rates at doses that had no significant effect on behavior maintained by an identical schedule of stimulus termination. The neurochemical bases of the observed drug interactions on behavior were investigated further using in vivo microdialysis techniques in a separate group of awake monkeys to monitor drug-induced changes in extracellular dopamine (DA). Cocaine (1.0 mg/kg) elevated the concentration of DA in the caudate nucleus to approximately 300% of basal levels. Pretreatment with alaproclate or quipazine attenuated cocaine-induced increases in extracellular DA at the same pretreatment doses that decreased cocaine self-administration. The results obtained suggest that increasing brain 5-HT activity can attenuate the reinforcing effects of cocaine, ostensibly by decreasing the ability of cocaine to elevate extracellular DA in brain areas that mediate the behavioral effects. These findings extend those reported previously for the behavioral-stimulant effects of cocaine and identify a potential neurochemical mechanism underlying drug interactions on behavior.Abuse of stimulant drugs such as cocaine persists as a major health problem in the United States (Chilcoat and Johanson, 1998). Clearly, there is a great need for pharmacological treatments to combat abuse of these drugs; however, no pharmacotherapy has demonstrated sufficient efficacy for widespread clinical use (Carroll et al., 1999). A better understanding of the effects of cocaine on central nervous system neurochemistry will help identify effective approaches in developing medications for treating cocaine dependence.The behavioral-stimulant and reinforcing effects of cocaine have been linked to its ability to enhance dopaminergic neurotransmission by inhibiting DA uptake via transporter blockade (Ritz et al., 1987). The affinities of several cocainelike drugs for DA transporter correlate well with their potencies for supporting self-administration behavior (Ritz et al., 1987;Bergman et al., 1989). In humans, a significant correlation has been observed between DA transporter binding and the intensity of subjective effects produced by intravenous cocaine (Volkow et al., 1997). Cocaine affects neurotransmission in various brain DA systems, leading to a variety of behavioral effects. For example, the DA neurons of the substantia nigra pars compacta project to the caudate nucleus and putamen, the primate homologues of the rodent dorsal striatum (Parent et al., 1995), to modulate motor function. Facilitation of DA transmission in the nigrostriatal system...

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Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats

Cited by 109 publications

References 21 publications

Mechanisms of Acute Cocaine Toxicity

Mechanisms of Acute Cocaine Toxicity

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

Serotonergic Attenuation of the Reinforcing and Neurochemical Effects of Cocaine in Squirrel Monkeys

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