Addiction may be defined as habitual psychological and
physiological dependence on a substance or practice beyond one's
voluntary control. The various neurotransmitters like dopamine and
reward pathways linked to the limbic system play an important role in
addiction.Brain Chemicals: Serotonin is produced by nuclei
in the median raphe of the brain stem. Serotonin acts as a inhibitor of
pain pathways in the spinal cord and controls a person’s mood and even
cause sleep. Another important chemical in the brain is GABA
(gamma-amino-butyric-acid), which is secreted by the nerve terminals in
the spinal cord, cerebellum, basal ganglia, and many areas of the
cortex. GABA causes inhibition. Norepinephrine is secreted by neurons
in the brain stem, hypothalamus and postganglionic neurons of
sympathetic nervous system. It helps to control the overall mood and
activity of the mind. At the postganglionic neurons, it may excite some
organs or inhibit others. Dopamine is secreted by the neurons that
originate in the substantia nigra. The effect of dopamine is usually
inhibition. The Limbic System:The limbic system is a group of
brain structures that are involved in various emotions such as
aggression, fear, pleasure and also in the formation of memory. The
limbic system affects the endocrine system and the autonomic nervous
system. It is comprised of several subcortical structures located
around the thalamus.
Mechanisms
of Addiction: Tolerance: can be defined as the reduced response to a
drug following repeated exposures to the drug. Sensitisation: an
exaggerated response to a drug because of prior exposure to that
drug Withdrawal: symptoms (usually aversive) that accompany the
abrupt cessation of drug use.
The Biological Basis of Addiction: Although personality, social,
and genetic factors may be important factors, the pharmacological
activation of brain reward systems is largely responsible for producing
a drug's potent addictive properties. Nonpharmacological factors are
likely to be important in influencing initial drug use and in
determining how rapidly an addiction develops. Mesolimbic
Dopamine Neurons:Dopamine is a neurotransmitter, which has a
significant role in the regulation of mood and affect as well as in the
motivation and reward processes. Although the brain has numerous
dopamine systems, the mesolimbic dopamine system is the most important
for motivational processes. By enhancing the mesolimbic dopamine
activity, some addictive drugs produce their potent effects on
behaviour. Heroin-Enhanced Dopamine Activity: The rate of neuronal firing by
dopamine cells is increased by Heroin, which produce an increase in
dopamine release. Because of this enhanced dopamine activity, the
heroin user experiences mood elevation and euphoria. As the
pharmacological action ceases, the drug user is highly motivated to
repeat the experience.
Cocaine-Enhanced Dopamine Activity: The reuptake of dopamine is
inhibited by Cocaine, which increases dopamine availability in the
synapse and increases dopamine's action on the postsynaptic neurons.
This causes mood elevation and euphoria. Since Cocaine's effect is
usually quite short, the user repeatedly administers cocaine to
re-experience its effects.
Combined Heroin- and Cocaine-Enhanced Dopamine Activity:Heroin and
cocaine can be combined to produce even more intense dopamine
activation. The heroin increases cell firing and dopamine release,
while the cocaine keeps the released dopamine in the synaptic cleft
longer thereby intensifying and prolonging its effects (popularly known
amongst users as speed-ball.)
Repeated use of cocaine or heroin can deplete dopamine. This causes
normal rewards to lose their motivational significance (i.e., produce
motivational toxicity). The mesolimbic dopamine system also
becomes more sensitive to pharmacological activation by psychomotor
stimulants and by opiates. These neuroadpative changes are probacritical for producing an addiction. Neurobiology of
pleasure and addiction: Pleasure can be described as a state or feeling
of happiness and satisfaction resulting from an experience that one
enjoys. Pleasure can serve to promote addiction. The process is a
complex neurobiological one, which relies on the reward circuitry or
limbic activity. These processes involve dopaminergic signaling.
Endorphins and endogenous morphinergic mechanisms may also play a role.
Addictive drugs are able to act directly on the reward pathways. Reward
pathways are linked to the brain’s limbic system. The euphoria induced
by drugs enhances the activity of the brain’s pleasure and reward
systems. The prefrontal or orbitofrontal cortices, cingulate gyrus,
amygdala, hippocampus and nucleus accumbens are all involved in the
reward physiology. The brain's pleasure centre is interconnected with a
structure known as the nucleus accumbens in the limbic system. The
nucleus accumbens is involved in the "high" a person experiences from
drugs. Thus, there is a biologically interconnection between pleasure,
the limbic system and reward circuitry. The hippocampus makes memories
of such feelings of pleasure, accessible to this circuitry. Neuroendocrine
pathways of addictive behaviour: It is well known that plasma
concentrations of neuroendocrine peptides are modulated by alcohol
intake. Recent research, however, suggest that the endocrine system not
only responds passively to alcohol intake but also actively modulates
alcohol intake behaviour. The hypothalamo-pituitary-adrenocortical
(HPA) axis, with low corticotrophin-releasing hormone (CRH) is being
associated with more intense craving and increased probability of
relapse after acute detoxification. The intensity of craving or the
intensity of the alcohol withdrawal syndrome may also be modulated by
leptin, β-endorphin and atrial natriuretic peptide (ANP), which
indirectly regulate the HPA system. Investigating Human Drug
Addiction: A team of researchers at The Massachusetts General Hospital
and Harvard Medical School are investigating the use of functional
magnetic resonance imaging (fMRI). This helps to observe the brains of
cocaine users while they are injected with cocaine. FMRI shows regional
changes, which accompany neuronal activity in specialized parts of the
brain, by providing rapid, high quality pictures of blood flow and
oxygen use. The researchers aim to relate dynamic changes in regional
brain activity to subjective responses measured at the same time.
They are also studying the brains of cocaine users while they have
a craving for cocaine. This study will lead to a greater understanding
of the psychobiological processes that cause compulsive drug use and
relapse. Scientists are also doing research with a mammalian model of
emotion (i.e. rodent ultrasonic vocalizations) to predict drug-related
phenomena such as abuse potential, anatomical location of mediating
neural substrates, and the psychological impact of withdrawal.