Biology Reference
In-Depth Information
drug. These persistent effects reflect long-term neuroplastic changes in the neural circuitry
related to conditioned cocaine effects.
A crucial consequence of drug addiction, often reported by addicts in clinical settings, is
the reduced interest in natural rewards, such as sex. In fact, one of the diagnostic criteria for
drug addiction is the narrowing interest in different activities that previously were an
important part of the person's life. When cocaine users are examined with functional
neuroimaging techniques using sex images and cocaine-related images, sex (natural reward)
induced less activation in cerebral circuitry than cocaine (Garavan et al., 2000). Similar
results were reported in studies of cocaine self-administration in rats in which cocaine
produced increases in brain stimulation reward thresholds during withdrawal (Markou and
Koob, 1991). This finding has important implications and suggests that the effects of cocaine
in narrowing the user's interests in life have a neurobiological background. In fact, cocaine
craving is subserved by the same cerebral regions that are activated by natural rewarding and
reward-evocative stimuli; this could indicate a rewriting of normal, emotionally-driven
preferences. These neurobiological changes may have important consequences for decision-
making because the decreased response to natural rewards may be exacerbated during
craving, further increasing the desire for cocaine (Robbins and Everitt, 1999)
.
Together these findings suggest that the emotional and behavioral consequences in the
development of addiction can result from changes in long-term synaptic plasticity, including
reduced activity in the prefrontal cortex, reduced D2 expression in the striatum, increased
responsiveness for cocaine related cues and decreased responsiveness for natural rewarding
stimuli. These neuroplastic changes may play an important role in the feeling of craving that
accompanies addiction and relapse.
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Addiction is not triggered instantaneously after the exposure to cocaine. On the contrary,
the development of addiction involves neural adaptations that develop with different temporal
courses ranging from hours to days to months. The VTA is considered to be essential for the
development of behavioral sensitization, one of the models of drug addiction. Behavioral
sensitization can be defined as a progressive increase of some behavioral effects of the drug,
such as locomotor activity with repeated cocaine doses. Behavioral sensitization is considered
a model useful for studying the rewarding and addictive effects of cocaine (Kalivas, 1995).
The usual procedure to study behavioral sensitization is based either on passive cocaine
injection of rodents (i.e. mice or rats) or intravenous self-administration of cocaine by such
rodents themselves in an operant chamber. Before starting the program, spontaneous
individual activity is measured in an activity chamber where the animals were placed during a
stipulated time period. The program continues for approximately 6 to 15 days approximately.
Each day, rodents get their programmed dose of cocaine. In the passive cocaine injection,
rodents usually receive a dose of 15 mg/kg intraperitoneal (i.p.). In the self-administration
program, cocaine is usually administered in doses of 0.75 mg/kg per infusion, and in each
session rats get a total of 10 infusion (i.e. 7.5 mg/kg) within and hour. There is always a
control group to compare with the cocaine-treated rodents. Following the sequence of
repeated, intermittent drug treatment, rodents are withdrawn from the drug over several days
