Early isolation linked to enhanced response to cocaine

Drug addiction affects millions of people around the world, causing numerous problems ranging from emotional and psychological difficulties to physical and health issues.

Initial drug use can be motivated by curiosity or peer pressure, but in some animals, such as rats, it can also be the result of a stressful early life event, such as social isolation. A new study examines the impact of social isolation on the animal's response to cocaine.

The study, Social Isolation During Perinatal Development Alters the Behavioral Response to Cocaine in Juvenile Rats, was conducted by Natasha Lugo-Escobar, Nicole Carreras and Annabell C. Segarra, University of Puerto Rico, School of Medicine, Rio Piedras, PR. The team will present its findings at the 122nd Annual Meeting of the American Physiological Society (APS; www.the-aps.org/press), which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.

The Study

Drugs of abuse act on the reward centers of the brain. These areas are normally involved in mediating pleasure, and also regulate the psycho-stimulant effects of drugs such as cocaine. Stress is known to enhance drug seeking behavior, as well as the psychostimulant effects of cocaine. Since rats are social animals, isolation was used as a stressor to explore the association between stress during development and susceptibility to the psychostimulant effects of drugs of abuse, such as cocaine.

Rats were stressed: (1) as fetuses (by housing the pregnant mother alone), (2) as neonates (by isolating newborn rats for 1 hr daily during the first 9 days of life) or as adolescents (by housing each rat separately during days 21-35). Two additional groups: (4) isolated as fetuses, neonates and adolescents and (5) controls - not isolated during any developmental period, comprised the 5 groups studied. When rats reached 21 days of age, they were weaned from their mothers and tested for the psychostimulant response to cocaine as well as for the development of sensitization, a phenomenon characterized by an increase response to the same amount of a drug over time. For 5 days, half of the rats from all groups were injected with saline and the other half with cocaine (15 mg/kg). This was followed by a 7 day drug free period and an additional cocaine injection on day 13. Locomotor activity was measured on days 1, 5 and 13 immediately after injection.

Results

The researchers found that:

• Rats that were isolated during all three developmental periods, showed a higher locomotor response to cocaine than control rats.
• The study indicates that the developmental period most susceptible to isolation stress, particularly in males, is the neonatal period, since males isolated as neonates show an increase in the locomotor, and sensitized response to cocaine, compared to male control and to female rats.

Conclusions

This study suggests that isolation during early development alters the brain sensitivity to cocaine, such that when the animal reaches adolescence and is exposed to cocaine, it is more sensitive to the psychostimulant effects of the drug.

These studies contribute to understanding the mechanisms that may lead to greater abuse of drugs during adolescence.

Additional studies are planned.

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