Behavioural Pharmacology最新文献

Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30  μ g/paw), l -NAME (NO synthase inhibitor, 10 and 100  μ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200  μ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30  μ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0   μ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25  μ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.

Many structures of the central nervous system recruit different neurotransmitters in pain processing. This study focused on the contribution of histamine and its H 1 receptors in the ventral pallidum (VP) in mediating pain-triggered behaviors. Intra-VP microinjection of histamine and 2-pyridylethylamine (2-PEA, a histamine H 1 receptor agonist) at the same doses of 0.5 and 1 µg/200 nl reduced both the first and second phases of licking/biting duration as well as flinching number induced by intra-plantar (ipl) injection of formalin (2.5%, 50 µl). Premicroinjection of mepyramine (a histamine H 1 antagonist, 2 µg/200 nl) into the VP antagonized the suppressive effects of 1 µg/200 nl histamine and 2-PEA on licking/biting and flinching behaviors. The possible mechanisms of the above-mentioned pain-reducing effects were followed by intra-VP and intrathecal administration of naloxone (an opioid receptor antagonist). Naloxone (2 µg/200 nl) preadministration into the VP inhibited attenuating effects of histamine and 2-PEA on both the licking/biting and flinching behaviors, whereas intrathecal injection of naloxone only inhibited their suppressing effects on flinching behavior. None of the treatments used in this study altered the animal's motor activity. The obtained results may reveal the role of histamine and its activated H 1 receptor in the VP in suppressing the pain behaviors caused by formalin. Opioid receptors in the VP and spinal cord may contribute to these functions.

In 2016, the National Institutes of Health mandated the use of both male and female mice in funded research. The use of both sexes is an important variable to consider; however, it comes with negative consequences such as increased animal expenses. One way to combat these negatives is to explore the option of using a within-subjects design (repeated measures) in behavioral assays that historically use a between-subjects design. Our study aimed to determine if a within-subjects design can be utilized in the marble burying assay. The marble burying assay is used as a tool for screening putative anxiolytic compounds as the assay is thought to measure obsessive-compulsive disorder- or anxiety-like behaviors. First, we compared the effects of sex and digging medium (corn cob or Sani Chip) on the number of marbles buried using CD-1 mice. Second, we determined if mice would continue to bury marbles after repeated exposures to the test arena. Lastly, we tested three positive controls (buspirone, ketamine, and fluoxetine). We found that mice buried significantly more marbles within Sani Chip digging medium, and no sex differences were observed. Next, the number of marbles buried and locomotor activity remained consistent across four test sessions. The positive controls buspirone (3.2-10 mg/kg) ketamine (32 mg/kg), and fluoxetine (10 mg/kg) decreased the number of marbles buried using the within-subjects design. These data suggest that a within-subjects design is optimal for the marble burying assay as it will reduce the number of animals and increase statistical power.

COR659 is a new compound, the action of which is exerted via a dual mechanism: positive allosteric modulation of the GABAB receptor; antagonism or inverse agonism at the cannabinoid CB1 receptor. Recent lines of experimental evidence have indicated that COR659 potently and effectively reduced operant self-administration of and reinstatement of seeking behaviour for a chocolate-flavoured beverage. The present study was designed to assess whether the ability of COR659 to diminish these addictive-like, food-motivated behaviours extended to a rat model of overeating palatable food. To this end, rats were habituated to feed on a standard rat chow for 3 h/day; every 4 days, the 3-hour chow-feeding session was followed by a 1-hour feeding session with highly palatable, calorie-rich Danish butter cookies. Even though satiated, rats overconsumed cookies. COR659 (0, 2.5, 5, and 10 mg/kg, i.p.) was administered before the start of the cookie-feeding session. Treatment with all 3 doses of COR659 produced a substantial decrease in intake of cookies and calories from cookies. These results extend the anorectic profile of COR659 to overconsumption of a highly palatable food and intake of large amounts of unnecessary calories.

The Stroop Effect has been linked to social concept priming, suggesting that the latter may trigger automatic behaviour aligned with the primed concept. This study examined the effects of social priming on alcohol attentional bias, with a sample of mostly light drinkers; it used a social priming task and an alcohol-Stroop test to measure participants' response times (RTs) before and after they had been socially primed. Participants were separated into one of three social priming conditions: Neutral, Alcohol Addiction, and Alcohol Preoccupation. A mixed ANOVA was run to determine whether participants' RTs to alcohol-related stimuli, "rather than to neutral sitmuli," slowed significantly after the alcohol interference tasks, relative to the neutral interference task, suggesting an alcohol attentional bias had been induced by the social priming exercise. Key interaction terms did not reveal such an interaction, but rather a general slowing down (for both neutral and alcohol stimuli), in the Alcohol conditions, relative to the Neutral one. As a result, we can conclude that while we did not induce an alcohol-specific bias in participants, we did discover a generalised interference effect, following alcohol-related social priming tasks.

The psychostimulant drug methamphetamine (METH) causes euphoria in humans and locomotor hyperactivity in rodents by acting on the mesolimbic dopamine (DA) pathway and has severe abuse and addiction liability. Behavioral sensitization, an increased behavioral response to a drug with repeated administration, can persist for many months after the last administration. Research has shown that the serotonin 1B (5-HT1B) receptor plays a critical role in the development and maintenance of drug addiction, as well as other addictive behaviors. This study examined the role of 5-HT1B receptors in METH-induced locomotor sensitization using 5-HT1B knockout (KO) mice. To clarify the action of METH in 5-HT1B KO mice the effects of METH on extracellular levels of DA (DAec) and 5-HT (5-HTec) in the caudate putamen (CPu) and the nucleus accumbens (NAc) were examined. Locomotor sensitization and extracellular monoamine levels were determined in wild-type mice (5-HT1B +/+), heterozygous 5-HT1B receptor KO (5-HT1B +/-) mice and homozygous 5-HT1B receptor KO mice (5-HT1B -/-). Behavioral sensitization to METH was enhanced in 5-HT1B -/- mice compared to 5-HT1B +/+ mice but was attenuated in 5-HT1B +/- mice compared to 5-HT1B +/+ and 5-HT1B -/- mice. In vivo, microdialysis demonstrated that acute administration of METH increases DAec levels in the CPu and NAc of 5-HT1B KO mice compared to saline groups. In 5-HT1B +/- mice, METH increased 5-HTec levels in the CPu, and DAec levels in the NAc were higher than in others.5-HT1B receptors play an important role in regulating METH-induced behavioral sensitization.