Detailed analysis of food-reinforced operant lever pressing distinguishes effects of a cannabinoid CB1 inverse agonist and dopamine D1 and D2 antagonists

McLaughlin, Peter; Winston, Keisha M.; Swezey, Lynn A.; Vemuri, V. Kiran; Makriyannis, A.; Salamone, John D.

doi:10.1016/j.pbb.2010.04.009

Cited by 6 publications

(7 citation statements)

References 55 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, there is evidence that AM251 may act as CB 1 receptor antagonist at low concentrations and as inverse agonist at high concentrations [53,54]. In the present study AM251 was used at a dose of 1 mg/kg i.p., a dose that is controversially retained either evoke an inverse agonist response or block CB 1 receptors and prevent the effects of CB 1 agonists [55][56][57][58][59]. In short, it is challenging to discriminate in vivo the AM251 action as inverse agonist at the CB 1 receptor or antagonist blocking endogenous endocannabinoids acting at a constitutively active CB 1 receptor.…”

Section: Discussionmentioning

confidence: 99%

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

Laricchiuta

Balsamo

Fabrizio

et al. 2020

IJMS

View full text Add to dashboard Cite

To promote efficient explorative behaviors, subjects adaptively select spatial navigational strategies based on landmarks or a cognitive map. The hippocampus works alone or in conjunction with the dorsal striatum, both representing the neuronal underpinnings of the navigational strategies organized on the basis of different systems of spatial coordinate integration. The high expression of cannabinoid type 1 (CB1) receptors in structures related to spatial learning—such as the hippocampus, dorsal striatum and amygdala—renders the endocannabinoid system a critical target to study the balance between landmark- and cognitive map-based navigational strategies. In the present study, mice treated with the CB1-inverse agonist/antagonist AM251 or vehicle were trained on a Circular Hole Board, a task that could be solved through either navigational strategy. At the end of the behavioral testing, c-Fos immunoreactivity was evaluated in specific nuclei of the hippocampus, dorsal striatum and amygdala. AM251 treatment impaired spatial learning and modified the pattern of the performed navigational strategies as well as the c-Fos immunoreactivity in the hippocampus, dorsal striatum and amygdala. The present findings shed light on the involvement of CB1 receptors as part of the selection system of the navigational strategies implemented to efficiently solve the spatial problem.

show abstract

Section: Discussionmentioning

confidence: 99%

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

Laricchiuta

Balsamo

Fabrizio

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Overall responding (i.e., number of responses in each 30-min session) was analyzed using a 3 × 4 (treatment × level) repeated-measures analysis of variance (ANOVA). An interaction in this test would permit 3 × 4 repeated-measures ANOVA of variables within the operant session that could potentially discriminate between Treatments, as has been done previously (McLaughlin et al, 2005a(McLaughlin et al, , 2010). Significant interactions were followed by simple main effects of level; where these were significant, non-orthogonal planned comparisons (Keppel and Wickens, 2004) between Control and each of the three other Levels were used as a post hoc test.…”

Section: Discussionmentioning

confidence: 99%

“…Inter-response time (IRT, in ms) excluded responses resulting in reinforcement. As has been done previously, IRTs were limited in time to distinguish from longer pauses in responding (McLaughlin et al, 2005b(McLaughlin et al, , 2010; IRTs longer than 500 ms were recorded as response pause length (PL, in s), which was capped at 30 s.…”

Section: Discussionmentioning

confidence: 99%

“…Once established, response suppression caused by AM 6527 in the same subjects could be assessed simultaneously for the extent to which its effects better matched either nondrug manipulation. Similar microanalyses have been used to determine whether other response rate-altering manipulations affect behavior in similar or functionally distinct ways (Brown and Seiden, 1975; Carriero et al, 1998; Fowler et al, 1991; McLaughlin et al, 2010; Salamone et al, 1995; Varvel et al, 2002). We used AM 6527 because it is a newer neutral CB1 antagonist with oral bioavailability (Limebeer et al, 2010; Sink et al, 2009; Wills et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CB1 antagonism produces behaviors more consistent with satiety than reduced reward value in food-maintained responding in rats

et al. 2016

View full text Add to dashboard Cite

Cannabinoid CB1 antagonists are widely known to reduce motivation for food, but it is not known whether they induce satiety or reduce reward value of food. It may therefore be necessary to compare effects of altered satiety and reward food value in the same appetitive task, and determine whether CB1 antagonism produces a behavior pattern similar to either, both, or neither. A fine-grained analysis of fixed-ratio 10 (FR10) responding for palatable food initially included number and duration of, and between, all lever presses and food tray entries in order to differentiate the pattern of suppression of prefeeding from that caused by reducing the reward value of the pellets with quinine. Discriminant function analysis then determined that these manipulations were best differentiated by effects on tray entries, pellet retrieval latencies, and time of the first response. At 0.5 mg/kg, AM 6527 produced similar effects to reducing reward value, but at 1.0 and 4.0 mg/kg, effects were more similar to those when animals were satiated. We conclude that AM 6527 both reduced reward value and enhanced satiety, but as dose increased, effects on satiety became much more prominent. These findings contribute to knowledge about the behavioral processes affected by CB1 antagonism.

show abstract

“…Operant lever-pressing tasks, such as that used in Experiment 3, provide a sensitive and reliable assay for such investigations (e.g. McLaughlin et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054

McLaughlin¹,

Thakur²,

Vemuri³

et al. 2013

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Due to the ubiquity of the CB1 cannabinoid receptor throughout the nervous system, as well as the many potential therapeutic uses of CB1 agonist-based interventions, it is desirable to synthesize novel probes of the CB1 receptor. Here, the acute behavioral effects of systemic (i.p.) administration of the putative novel CB1 full agonist AM 4054 were tested in rats. In Experiment 1, a dose range (0.15625 – 1.25 mg/kg) of AM 4054 produced effects consistent with CB1 agonism in the cannabinoid tetrad of tasks in rats, including induction of analgesia, catalepsy, hypothermia, and locomotor suppression. These effects were reversed with the CB1-selective inverse agonist AM 251 in Experiment 2, indicating that AM 4054 produced CB1 receptor-mediated effects. Analysis of open-field activity indicated that the reduction in locomotion is more consistent with general motor slowing than anxiogenesis. AM 4054 (0.0625 – 0.5 mg/kg) also dose-dependently reduced fixed-ratio 5 (FR5) operant responding for food in Experiment 3, and microanalysis of the timing and rate of lever pressing indicated a pattern of suppression similar to other CB1 agonists. Minimum doses of AM 4054 (0.125 – 0.3125 mg/kg) required to produce significant effects in these behavioral assays were lower than those of many CB1 agonists. It is likely that AM 4054 is a potent pharmacological tool for assessment of cannabinoid receptor function.

show abstract

Detailed analysis of food-reinforced operant lever pressing distinguishes effects of a cannabinoid CB1 inverse agonist and dopamine D1 and D2 antagonists

Cited by 6 publications

References 55 publications

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

CB1 antagonism produces behaviors more consistent with satiety than reduced reward value in food-maintained responding in rats

Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054

Contact Info

Product

Resources

About