Epidemiological studies have shown that people who begin experimenting drugs of abuse during adolescence are more likely to develop substance use disorders, and the earliest is the beginning of their use, the greatest is the likelihood to become dependent. Understanding the neurobiological changes increasing adolescent vulnerability to drug use is becoming imperative. Although all neurotransmitter systems undergo relevant developmental changes, dopamine system is of particular interest, given its role in a variety of functions related to reward, motivation, and decision making. Thus, in the present study, we investigated differences in mesolimbic and nigrostriatal dopamine transmission between adolescent (5, 6, 7 weeks of age) and adult rats (10‐12 weeks of age), in basal conditions and following drug challenge, by using in vivo brain microdialysis. Although no significant difference between adolescents and adults was observed in dopamine basal levels in the nucleus accumbens (NAc)shell and core, reduced DA levels were found in the dorsolateral striatum (DLS) of early and mid‐adolescent rats. Adolescent rats showed greater increase of dopamine in the NAc shell following nicotine (0.4 mg/kg), THC (1.0 mg/kg), and morphine (1.0 mg/kg), in the NAc core following nicotine and morphine, and in the DLS following THC, morphine, and cocaine (10 mg/kg). These results, while adding new insight in the development and functionality of the dopamine system during different stages of adolescence, might provide a neurochemical basis for the greater vulnerability of adolescents to drugs of abuse and for the postulated gateway effect of nicotine and THC toward abuse of other illicit substances.

A purple acid phosphatase was purified to homogeneity from Euphorbia characias latex. The native protein has a molecular mass of 130 ± 10 kDa and is formed by two apparently identical subunits, each containing one Fe(III) and one Zn(II) ion. The two subunits are connected by a disulfide bridge. The enzyme has an absorbance maximum at 540 nm, conferring a characteristic purple color due to a charge-transfer transition caused by a tyrosine residue (Tyr172) coordinated to the ferric ion. The cDNA nucleotide sequence contains an open reading frame of 1392 bp, and the deduced sequence of 463 amino acids shares a very high degree of identity (92-99%) to other purple acid phosphatases isolated from several higher plants. The enzyme hydrolyzes well p-nitrophenyl phosphate, a typical artificial substrate, and a broad range of natural phosphorylated substrates, such as ATP, ADP, glucose-6-phosphate, and phosphoenolpyruvate. The enzyme displays a pH optimum of 5.75 and is inhibited by molybdate, vanadate, and Zn2+, which are typical acid phosphatase inhibitors.

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Smoking during adolescence may increase the likelihood to develop nicotine dependence and to abuse other drugs such as cocaine. Despite great efforts to understand underlying neurobiological mechanisms of this progression, less attention has been paid to the role of genetic factors. Here, we investigated the influence of both genetic background and age at first nicotine exposure in the long‐lasting effects on mesolimbic dopamine transmission including the increased cocaine‐rewarding effect. Mid‐adolescent and adult rats of inbred strains Lewis (addiction prone) and Fischer 344 (addiction resistant) were administered nicotine (0.4 mg/kg) or vehicle once daily for 5 days. Changes in dopamine transmission were investigated by in vivo microdialysis and electrophysiology after 30 days of withdrawal, whereas changes in cocaine‐rewarding effect were assessed via conditioned place preference paradigm. Nicotine pre‐exposure differentially changed mesolimbic dopamine transmission depending on strain and age of pre‐exposure. A potentiation of dopamine response to nicotine was observed in nucleus accumbens (NAc) core of both strains and age groups, whereas dopamine response in NAc shell was enhanced exclusively in Lewis rats exposed to nicotine during adolescence. A similar response was observed following cocaine challenge at adulthood. Changes in VTA dopamine cell population and activity were observed only in adolescent nicotine‐pretreated Lewis rats, which also showed an increased cocaine‐rewarding effect at adulthood. These results highlight the influence of genetic background in the long‐lasting effects of nicotine exposure and suggest that exposure during adolescence might increase nicotine and cocaine‐rewarding properties in genetically vulnerable individuals, thereby facilitating progression toward dependence.

Genetic background and age at first exposure have been identified as critical variables that contribute to individual vulnerability to drug addiction. Evidence shows that genetic factors may account for 40–70% of the variance in liability to addiction. Alcohol consumption by young people, especially in the form of binge-drinking, is becoming an alarming phenomenon predictive of future problems with drinking. Thus, the literature indicates the need to better understand the influence of age and genetic background on the development of alcohol dependence. To this aim, the inbred rat strains Lewis (LEW, addiction prone) and Fischer 344 (F344, addiction resistant) were used as a model of genetic vulnerability to addiction and compared with the outbred strain Sprague-Dawley (SD) in a two-bottle choice paradigm as a model of alcohol abuse. During a 9-week period, adolescent and adult male rats of the three strains were intermittently exposed to ethanol (20%) and water during three 24-h sessions/week. Adult and adolescent SD and LEW rats escalated their alcohol intake over time reaching at stable levels, while F344 rats did not escalate their intake, regardless of age at drinking onset. Among adolescents, only F344 rats consumed a higher total amount of ethanol than adults, although only SD and LEW rats escalated their intake. Adult LEW rats, albeit having a lower ethanol consumption as compared to SD rats but greater than F344, showed a more compulsive intake, consuming higher amounts of ethanol during the first hour of exposure, reaching a higher degree of ethanol preference when start drinking as adolescents. Behavioral analysis during the first hour of ethanol consumption revealed significant strain differences, among which noticeable the lack of sedative effect in the LEW strain, at variance with F344 and SD strains, and highest indices of withdrawal (most notable jumping) in LEW rats during the first hour of abstinence days. The present results underscore the importance of individual genetic background and early onset of alcohol use in the progression toward abuse and development of alcohol addiction.