Comparison of the action of the 5-HT2 antagonists amperozide and trazodone on preference for alcohol in rats

Ba, McMillen; Walter, S; Hl, Williams; Myers, R.D.

doi:10.1016/0741-8329(94)90032-9

Cited by 21 publications

(8 citation statements)

References 33 publications

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“…However, the effects of SERT KO are rather complex and can also increase the rewarding effects of cocaine (Sora et al , 1998; Hall et al , 2002; Hall et al , Submitted). This should not be surprising given the diverse effects that pharmacological treatments aimed at specific serotonin receptor subtypes have on drug reward, including both increases and decreases in the rewarding effects of diverse classes of addictive drugs (Carboni et al , 1989; Fadda et al , 1991; Higgins et al , 1992a; Higgins et al , 1992b; Bisaga et al , 1993; Kostowski et al , 1993; Lu et al , 1994; McMillen et al , 1994; Tomkins et al , 1994a; Tomkins et al , 1994b; Rompre et al , 1995; Tomkins et al , 1995; Parsons et al , 1998; Wilson et al , 1998; Fletcher & Korth, 1999; Harrison et al , 1999; Maurel et al , 1999; Tomkins & O'Neill, 2000; Fletcher et al , 2004). Indeed, under some circumstances (e.g.…”

Section: Introductionmentioning

confidence: 99%

Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice

Hall

Randall-Thompson

et al. 2009

Neuroscience

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The behavioral effects of cocaine are affected by gene knockout of the dopamine transporter (DAT), the serotonin transporter (SERT) and the norepinephrine transporter (NET). The relative involvement of each of these transporters varies depending on the particular behavioral response to cocaine considered, as well as on other factors such as genetic background of the subjects. Interestingly, the effects of these gene knockouts on cocaine induced locomotion are quite different from those on reward assessed in the conditioned place preference paradigm. To further explore the role of these genes in the rewarding effects of cocaine, the ability of five daily injections of cocaine to induce conditioned locomotion was assessed in DAT, SERT and NET knockout (KO) mice. Cocaine increased locomotor activity acutely during the initial conditioning session in SERT KO and NET KO, but not DAT KO, mice. Surprisingly, locomotor responses in the cocaine-paired subjects diminished over the 5 conditioning sessions in SERT KO mice, while locomotor responses increased in DAT KO mice, despite the fact that they did not demonstrate any initial locomotor responses to cocaine. Cocaine-induced locomotion was unchanged over the course of conditioning in NET KO mice. In the post-conditioning assessment, conditioned locomotion was not observed in DAT KO mice, and was reduced in SERT KO and NET KO mice. These data reaffirm the central role of dopamine and DAT in the behavioral effects of cocaine. Furthermore, they emphasize the polygenic basis of cocaine mediated behavior and the non-unitary nature of drug reward mechanisms, particularly in the context of previous studies that have shown normal cocaine conditioned place preference in DAT KO mice.

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Section: Introductionmentioning

confidence: 99%

Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice

Hall

Randall-Thompson

et al. 2009

Neuroscience

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“…These studies show that, at the dose mentioned above, mirtazapine (Salazar-Juarez et al Regarding the effect of trazodone and pindolol, our results differed from those reported by other researchers. Trazodone and pindolol did not affect the expression of locomotor sensitization to cocaine (McMillen et al, 1994).…”

Section: Discussionmentioning

confidence: 71%

Evaluation of Multi-target Drugs on the Cocaine-induced Locomotor Sensitization in Rats

Barbosa-Méndez

Salazar-Juárez

2022

Preprint

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Purpose — Cocaine use disorder (CUD) is a complex disease. Some suggest that multi-target drugs could be useful in the treatment of cocaine use disorder. Several studies have shown the efficacy of various multi-target-target drugs used in clinical studies to treat CUD; which integrate into their pharmacological profile the simultaneous NE or 5-HT receptors antagonism or agonism. However, the results of these studies have not shown results consistently. Thus, this study aimed to compare the efficacy of various multi-target drugs on cocaine-induced behavioral effects in rats. Methods — Male Wistar rats received cocaine (10 mg/Kg; i.p.) during the induction and expression of locomotor sensitization. The MIR, PIN, FLX, RIS, TRZ, ZRP, OND, YOH, or PRZ were administered 30 minutes before cocaine. After each treatment, the locomotor activity was recorded for 30 minutes. In experiments 5 and 6, the animals were sacrificed after treatment administration. Dopamine levels were determined in the ventral striatum, the prefrontal cortex (PFc), and the ventral tegmental area (VTA) by high-performance liquid chromatographic (HPLC) in animals treated with mirtazapine and cocaine. The quantification of c-fos immunoreactive cells was carried out by stereology analysis. Results — In this study, we found mirtazapine generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration compared to the other drugs evaluated. Also, at the optimal doses used the PIN, FLX, RIS, TRZ, ZRP, OND, YOH, or PRZfailed to attenuate long-term cocaine locomotor activation. In addition, mirtazapine decreased in the striatum, prefrontal cortex (PFc), and ventral-tegmental area (VTA) the amount of cocaine-induced extracellular dopamine and the number of cells immunoreactive to the Fos protein. Conclusion — At the optimal doses of drugs evaluated, mirtazapine was the multi-target drug that showed the greatest long-term effects on cocaine-induced behavioral effects compared to other multi-target drugs.

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“…1992(Myers et ul. & 1993McMillen et al 1994). Amperozide remains an interesting putative adjunct to the psychotherapy of substance abuse.…”

Section: Discussionmentioning

confidence: 99%

The Cardiovascular Effects of Amperozide: Interactions with Cocaine

Jones

McMillen

1999

Pharmacology & Toxicology

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Absrrwcr: Amperozide is a 5-HTZA receptor antagonist that significantly reduces the acquisition and expression, by rats, of a cocaine conditioned place preference. In order to rule out the possibility that amperozide affects a cocaine conditioned place preference due to effects on blood pressure or heart rate, the cardiovascular effects of amperozide were investigated. Alternating cumulative doses of amperozide (0.5, 1.0, 1.5 and 2.5 nig kg-l) or saline and phenylephrine (8 pg kg-I) were administered through the femoral vein of awake freely-moving Sprague-Dawley rats and blood pressure and heart rate were recorded from the femoral artery. A single dose of cocaine (5.0 mg kggl) was administered after all the amperozide or saline doses were given. Amperozide (0.5, 1.0, I .5 and 2.5 mg kg-I) did not have any significant effect on blood pressure compared to the saline control treatment to the same animals. However, 0.5 mg kg-I amperozide significantly decreased heart rate at 5 and 10 min. after administration, but higher doses did not further depress heart rate. Amperozide did not affect the increased blood pressure and decreased heart rate caused by phenylephrine, an al-adrenoceptor agonist. In addition, amperozide did not affect the cardiovascuhr response to an intravenous dose of 5.0 nig kg-I cocaine. These results suggest that amperozide does not cause direct cardiovascular effects. The mechanism by which the lowest dose of amperozide caused a decrease in heart rate is unknown. Amperozide affects neither a-adrenoceptor mediated vasoconstriction nor the increased sympathetic activity caused by the peripheral and central effects of cocaine. The significance of these results, in terms of locomotor activity and the cocaine conditioned place preference paradigm, is discussed.Amperozide is a novel putative antipsychotic drug characterized by high affinity for 5-hydro~ytryptamine~~ ( 5 -HTzA) receptors (Axelsson ef u/. 1991; Bjork et ul. 1992). Amperozide also has moderate affinity for a,-adrenergic receptors, a weak affinity for D2 dopamine receptors (Svartengren & Simonsson 1990; McMillen et nl. 1993) In a behavioural model used to study drug addiction, amperozide significantly reduced a cocaine-induced conditioned place preference (Jones & McMillen 1995). This report demonstrated that animals spent significantly more time in the cocaine associated chamber after repeated cocaine administration compared to the time spent in the cocaine-associated chamber before cocaine administration. Administration of amperozide prior to each dose of cocaine during the conditioning phase completely blocked a conditioned place preference. The mechanism by which amperozide reduced the cocaine-conditioned place preference is unknown. It is hypothesized that amperozide acts within the mesocorticolinibic system to inhibit the rewarding effects related to cocaine-associated conditioning cues, without a blockade of dopamine receptors (Jones & McMillen 1995). In the conditioned place preference paradigm, drugs are injected on training days...

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Comparison of the action of the 5-HT2 antagonists amperozide and trazodone on preference for alcohol in rats

Cited by 21 publications

References 33 publications

Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice

Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice

Evaluation of Multi-target Drugs on the Cocaine-induced Locomotor Sensitization in Rats

The Cardiovascular Effects of Amperozide: Interactions with Cocaine

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