Behavioral economics of cocaine self-administration in male and female rats.

There are sex differences in the development of cocaine addiction. For example, the time that it takes for women from initial use to addiction is significantly shorter than for men. Thus, understanding why females are more vulnerable to cocaine addiction will provide insights into sex differences in the mechanisms underlying cocaine addiction.

c-Jun N terminal kinase signaling pathways mediate cannabinoid tolerance in an agonist-specific manner.

Tolerance to the antinociceptive effects of cannabinoids represents a significant limitation to their clinical use in managing chronic pain. Tolerance likely results from desensitization and down-regulation of the cannabinoid type 1 receptor (CBR), with CBR desensitization occurring via phosphorylation of CBRs by a G protein-coupled receptor kinase and subsequent association with an arrestin protein. Previous studies have shown that (1) desensitization-resistant S426A/S430A mice exhibit a modest delay in tolerance for Δ-THC and (-)-CP55,940 but a more pronounced disruption in tolerance for WIN 55,212-2 and (2) that c-Jun N-terminal kinase (JNK) signaling may selectively mediate antinociceptive tolerance to morphine compared to other opioid analgesics.

Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain.

The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain.

Tolerance to the antinociceptive and hypothermic effects of morphine is mediated by multiple isoforms of c-Jun N-terminal kinase.

The abuse and overdose of opioid drugs are growing public health problems worldwide. Although progress has been made toward understanding the mechanisms governing tolerance to opioids, the exact cellular machinery involved remains unclear. However, there is growing evidence to suggest that c-Jun N-terminal kinases (JNKs) play a major role in mu-opioid receptor regulation and morphine tolerance.

Morphine-induced antinociception and reward in "humanized" mice expressing the mu opioid receptor A118G polymorphism.

The rewarding and antinociceptive effects of opioids are mediated through the mu-opioid receptor. The A118G single nucleotide polymorphism in this receptor has been implicated in drug addiction and differences in pain response. Clinical and preclinical studies have found that the G allele is associated with increased heroin reward and self-administration, elevated post-operative pain, and reduced analgesic responsiveness to opioids.

Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.

Background: Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists.