Mice from the inbred C57BL/6 strain have been commonly used for the generation and analysis of transgenic and knockout animal models. However, several C57BL/6 substrains exist, and these are genetically and phenotypically different. In addition, each of these substrains can be purchased from different animal providers and, in some cases, they have maintained their breeding stocks separated for a long time, allowing genetic differences to accumulate due to individual variability and genetic drift. With the aim of describing the differences in the genotype of several C57BL/6 substrains, we applied the Illumina(®) Mouse Medium Density Linkage Mapping panel, with 1,449 single nucleotide polymorphisms (SNPs), to individuals from ten C57BL/6-related strains: C57BL/6JArc, C57BL/6J from The Jackson Lab, C57BL/6J from Crl, C57BL6/JRccHsd, C57BL/6JOlaHsd, C57BL/6JBomTac, B6(Cg)-Tyr ( c-2j )/J, C57BL/6NCrl, C57BL/6NHsd and C57BL/6NTac. Twelve SNPs were found informative to discriminate among the mouse strains considered. Mice derived from the original C57BL/6J: C57BL/6JArc, C57BL/6J from The Jackson Lab and C57BL/6J from Crl, were indistinguishable. Similarly, all C57BL/6N substrains displayed the same genotype, whereas the additional substrains showed intermediate cases with substrain-specific polymorphisms. These results will be instrumental for the correct genetic monitoring and appropriate mouse colony handling of different transgenic and knockout mice produced in distinct C57BL/6 inbred substrains.

The initial peopling of the Americas is a contested and evolving topic 1 , with the exact timing of the first arrivals still unknown. Historically, Mexico's understudied and controversial archaeological record has remained on the periphery of First Americans research 2 . However, in recent years, investigations have shown reliable evidence of a late-Pleistocene and early-Holocene human presence in the northwest region 3,4 , the Chiapas Highlands 5 , Central Mexico 6 , and the Caribbean coast [7][8][9] . Evidence of human presence at Chiquihuite Cave extends this antiquity and attests to the cultural variability of older-than-Clovis sites [10][11][12][13][14][15][16][17] and the earliest humans on the continent. Site settings and excavation context.

Although the first studies regarding the endogenous opioid system and addiction were published during the 1940s, addiction and cannabinoids were not addressed until the 1970s. Currently, the number of opioid addiction studies indexed in PubMed-Medline is 16 times greater than the number of cannabinoid addiction reports. More recently, functional interactions have been demonstrated between the endogenous cannabinoid and opioid systems. For example, the cannabinoid brain receptor type 1 (CB1) and mu opioid receptor type 1 (MOR1) co-localize in the same presynaptic nerve terminals and signal through a common receptor-mediated G-protein pathway. Here, we review a great variety of behavioral models of drug addiction and alcohol-related behaviors. We also include data providing clear evidence that activation of the cannabinoid and opioid endogenous systems via WIN 55,512-2 (0.4-10 mg/kg) and morphine (1.0-10 mg/kg), respectively, produces similar levels of relapse to alcohol in operant alcohol self-administration tasks. Finally, we discuss genetic studies that reveal significant associations between polymorphisms in MOR1 and CB1 receptors and drug addiction. For example, the SNP A118G, which changes the amino acid aspartate to asparagine in the MOR1 gene, is highly associated with altered opioid system function. The presence of a microsatellite polymorphism of an (AAT)n triplet near the CB1 gene is associated with drug addiction phenotypes. But, studies exploring haplotypes with regard to both systems, however, are lacking.

The classical dopamine D2 receptor has been widely studied in alcoholism. Recently, different studies have explored the role of the CB1 receptor in alcohol-related behavior. In alcohol addiction, relapse is one of the central features. In light of this, we investigated the functional roles of and interactions between CB1 and D2 receptors in alcohol relapse. We used the learned task of alcohol operant self-administration in Wistar rats. In order to evaluate alcohol relapse, we set up a protocol essentially based on the alcohol deprivation effect. We found that subchronic activation of CB1 (WIN 55,212-2, 2 mg/kg), but not D2 receptors (quinpirole, 1 mg/kg), during a period of alcohol deprivation increased long-lasting alcohol relapse. The cannabinoid-induced potentiation of alcohol relapse was mediated by a motivational and appetitive component, and not merely by alcohol consumption. This potentiation was prevented by the pharmacological inactivation of D2 receptors (raclopride, 0.1-0.3 mg/kg). Together, these results essentially demonstrate that activation of CB1 receptors plays a key role in the increase of alcohol relapse, whereas inactivation of D2 receptors modulates this aberrant behavior. We suggest that there exists a functional and interactive relationship between both receptor systems, which controls alcohol relapse and alcohol-learned tasks.

Repeated cocaine treatment followed by withdrawal protected against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.