Oxytocin and neuroadaptation to cocaine
by
Sarnyai Z
Laboratory of Neuroendocrinology,
Rockefeller University,
New York, NY, USA.
sarnysz@rockvax.rockefeller.edu
J Neuroendocrinol 1999 Oct; 11(10):765-9
ABSTRACT
Oxytocin (OT) has been implicated in neuroadaptive
processes such as learning, memory, and social-affiliative behavior as well
as in the regulation of physiological responses leading to adaptation to
the changing external and internal environment. Drugs of abuse constitute
a major challenge to the homeostasis of the body and behavior. Drug tolerance,
dependence and addiction may involve neuroadaptive mechanisms related to
learning and memory at cellular and systems levels. Considerable effort
has been made toward the understanding the neurobiological mechanisms of
addictive behavior. Neuropeptides OT and vasopressin (VP) might be involved
in these processes based on their effects on neuroadaptation and on their
neuroanatomical localization and pharmacological actions. It has been demonstrated
that both OT and VP have modulatory effects on opiate and alcohol tolerance
and dependence. This chapter summarize the effects of OT, and in lesser
extent VP, on neuroadaptation to cocaine, a psychostimulant drug of abuse.
We have shown that OT inhibits acute cocaine-induced locomotor hyperactivity,
exploratory activity and stereotyped behavior in rodents. Furthermore, OT
facilitated, whereas VP inhibited the development of behavioral sensitization
to cocaine. In a different model, OT inhibited the development of tolerance
to the stereotyped behavior-inducing effects of cocaine as well as cocaine
intravenous self-administration in rats. We demonstrated that OT acts through
its specific receptors in the basal forebrain and in the hippocampus. OT
and VP contents in the hypothalamus and limbic structures were altered by
acute and chronic cocaine administration in a dose-dependent and region-selective
manner. The differential plasticity of the brain OT-ergic and VP-ergic neurotransmissions
in response to cocaine may underlie the differences in the involvement of
these neuropeptides in cocaine addiction. Interaction of OT with dopaminergic
neurotransmission in the nucleus accumbens, a key brain structure in drug
addiction, as well as OT-ergic regulation of hippocampal processes may be
among the mechanisms of action through which OT modulates neuroadaptation
to cocaine. A better understanding of the role of OT in neuroadaptation
to cocaine may provide an insight into both the mechanisms of neuropeptide
actions in the brain as well as into the neurobiology of drug addiction.
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