Development of a novel alcohol and nicotine concurrent access (ANCA) self-administration procedure in baboons

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

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S03-3vulnerability to voluntary binge drinking in rats using an operant self-administration procedure

Alcohol and Alcoholism ◽

10.1093/alcalc/agx075.10 ◽

2017 ◽

Vol 52 (suppl_1) ◽

pp. i4-i30

Author(s):

Jeanblanc Jérôme ◽

Legastelois Rémi ◽

González-Marín Maria del Carmen ◽

Sauton Pierre ◽

Lebourgeois Sophie ◽

...

Keyword(s):

Binge Drinking ◽

Self Administration ◽

Administration Procedure

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A neural substrate of compulsive alcohol use

Science Advances ◽

10.1126/sciadv.abg9045 ◽

2021 ◽

Vol 7 (34) ◽

pp. eabg9045

Author(s):

Esi Domi ◽

Li Xu ◽

Sanne Toivainen ◽

Anton Nordeman ◽

Francesco Gobbo ◽

...

Keyword(s):

Large Population ◽

Brain Network ◽

Alcohol Addiction ◽

Central Nucleus ◽

Inhibitory Neurons ◽

Self Administration ◽

Core Element ◽

Neural Substrate ◽

Activity Dependent ◽

Administration Procedure

Alcohol intake remains controlled in a majority of users but becomes “compulsive,” i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.

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