Self-administration of orally-delivered phencyclidine and ethanol under concurrent fixed-ratio schedules in rhesus monkeys

1987 ◽  
Vol 93 (1) ◽  
pp. 1-7 ◽  
Author(s):  
M. E. Carroll
2007 ◽  
Vol 18 (2) ◽  
pp. 171-175 ◽  
Author(s):  
Chad M. Galuska ◽  
Tammy Wade-Galuska ◽  
James H. Woods ◽  
Gail Winger

2019 ◽  
Author(s):  
Matthew L Banks ◽  
Blake A. Hutsell ◽  
S Stevens Negus

ABSTRACTBackgroundIn drug addiction, relapse can be triggered by cues that function as discriminative stimuli to signal contingencies of drug availability and promote drug-taking behavior. Extinction procedures can weaken the association between drug-associated cues and drug use and may reduce the probability of relapse. This study evaluated effects of a regimen of extinction training on cocaine self-administration maintained in rhesus monkeys under a cocaine-vs.-food choice procedure that has been used previously to evaluate effectiveness of other candidate treatments for cocaine abuse.MethodsBehavior was initially maintained under a concurrent schedule of food delivery (1-g food pellets; fixed-ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection; fixed-ratio 10 schedule) during daily 2-h choice sessions in male rhesus monkeys (n=4). Subsequently, choice sessions were supplemented by daily 20-h extinction sessions for 14 consecutive days. During extinction sessions, cocaine-associated discriminative stimuli were presented, but responding did not produce cocaine injections. Cocaine continued to be available during choice sessions.ResultsPrior to extinction, cocaine maintained a dose-dependent increase in cocaine vs. food choice. Responding during extinction sessions declined to low levels by the fifth day. Exposure to extinction sessions produced a more gradual but significant decline in cocaine choice and a complementary increase in food choice during choice sessions.ConclusionsThese preclinical results support the effectiveness of extinguishing cocaine-associated discriminative stimuli as a non-pharmacological treatment strategy for reducing cocaine choice. Moreover, these results also support the construct validity of preclinical drug vs. food choice procedures as a tool for candidate treatment evaluation for cocaine addiction.


2010 ◽  
Vol 213 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Christopher A. Podlesnik ◽  
Mei-Chuan Ko ◽  
Gail Winger ◽  
Jürgen Wichmann ◽  
Eric P. Prinssen ◽  
...  

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.


Author(s):  
Zhanglei Dong ◽  
Bingwu Huang ◽  
Chenchen Jiang ◽  
Jiangfan Chen ◽  
Han Lin ◽  
...  

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.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2013 ◽  
Vol 20 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Shaolin Yang ◽  
Annabelle M. Belcher ◽  
Svetlana Chefer ◽  
D. Bruce Vaupel ◽  
Charles W. Schindler ◽  
...  

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