l-Stepholidine, a Naturally Occurring Dopamine D1 Receptor Agonist and D2 Receptor Antagonist, Attenuates Methamphetamine Self-Administration in Rats

Given the problems associated with the escalation in methamphetamine (METH) use, the identification of more effective treatment strategies is essential. l-stepholidine (l-SPD) is an alkaloid extract of the Chinese herb Stephania intermedia with dopamine D1 receptor partial agonistic and D2 receptor antagonistic dual actions. The unique pharmacological profile of l-SPD suggests that l-SPD may be effective for the treatment of METH addiction. The aim of this study was to characterize the effect of l-SPD on METH self-administration on a fixed-ratio 1 schedule. We found that 5 and 10 mg/kg of l-SPD attenuated METH self-administration behavior. These results demonstrate that l-SPD which possesses dual actions on dopamine D1 and D2 receptors, attenuates METH self-administration on a fixed-ratio 1 schedule.

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L-Stepholidine, a naturally occurring dopamine D1 receptor agonist and D2 receptor antagonist, attenuates heroin self-administration and cue-induced reinstatement in rats

Neuroreport ◽

10.1097/wnr.0000000000000012 ◽

2013 ◽

pp. 1 ◽

Cited By ~ 2

Author(s):

Kai Yue ◽

Baomiao Ma ◽

Lin Chen ◽

Xiang Tian ◽

Qin Ru ◽

...

Keyword(s):

Receptor Antagonist ◽

Receptor Agonist ◽

D2 Receptor ◽

Dopamine D1 Receptor ◽

D1 Receptor ◽

Self Administration ◽

Naturally Occurring

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D1 and D2 dopaminergic systems in the rat basolateral amygdala are involved in anxiogenic-like effects induced by histamine

Journal of Psychopharmacology ◽

10.1177/0269881111405556 ◽

2011 ◽

Vol 26 (4) ◽

pp. 564-574 ◽

Cited By ~ 22

Author(s):

Maryam Bananej ◽

Ahmad Karimi-Sori ◽

Mohammad Reza Zarrindast ◽

Shamseddin Ahmadi

Keyword(s):

Receptor Antagonist ◽

Receptor Agonist ◽

Basolateral Amygdala ◽

Dopamine D2 Receptor ◽

D2 Receptor ◽

Dopamine D1 Receptor ◽

D1 Receptor ◽

Dopamine D2 ◽

D1 And D2 Receptors ◽

Male Wistar Rats

Involvement of the dopamine receptors in the basolateral amygdala (BLA) in the effects of histamine on anxiety-like behaviors of the elevated plus maze in male Wistar rats was investigated. The results showed that bilateral intra-BLA injections of histamine (2.5, 5 and 7.5 µg/rat) induced an anxiogenic-like effect, revealed by decreases in percentage of open arm time (%OAT) and open arm entries (%OAE). Intra-BLA administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/rat), and dopamine D2 receptor agonist, quinpirole (0.03 and 0.05 µg/rat), decreased %OAT but not %OAE. Conversely, intra-BLA administration of dopamine D1 receptor antagonist, SCH23390 (0.5 and 1 µg/rat), and dopamine D2 receptor antagonist, sulpiride (0.3 and 0.5 µg/rat), increased %OAT and %OAE, suggesting an anxiolytic-like effect for both drugs. Interestingly, co-administration of a silent dose of SCH23390 or sulpiride prevented anxiogenic-like effects of SKF38393 and quinpirole, respectively. Conjoint administration of a sub-effective dose of SKF38393 (0.125 µg/rat) or quinpirole (0.01 µg/rat) along with lower doses of histamine (1 and 2.5 µg/rat) induced anxiolytic-like effects. On the other hand, intra-BLA pretreatment with a silent dose of SCH23390 (0.25 µg/rat) or sulpiride (0.1 µg/rat) prevented the anxiogenic-like effect of higher doses of histamine (5 and 7.5 µg/rat). No significant change was observed in total closed arm entries, as an index for motor activity of the animals. It can be concluded that the dopamine D1 and D2 receptors in the BLA may be involved in the anxiogenic-like effects induced by histamine.

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The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

Neurochemical Research ◽

10.1007/s11064-021-03238-9 ◽

2021 ◽

Author(s):

Zhanglei Dong ◽

Bingwu Huang ◽

Chenchen Jiang ◽

Jiangfan Chen ◽

Han Lin ◽

...

Keyword(s):

Nucleus Accumbens ◽

D2 Receptor ◽

Fixed Ratio ◽

Receptor Activation ◽

Addictive Behaviors ◽

Self Administration ◽

A2a Receptors ◽

Mediated Effects ◽

Seeking Behavior ◽

Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

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