Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.
Dopamine neurotransmission is associated with high susceptibility to cocaine abuse. Positron emission tomography was used in 12 rhesus macaques to determine if dopamine D2 receptor availability was associated with the rate of cocaine reinforcement, and to study changes in brain dopaminergic function during maintenance of and abstinence from cocaine. Baseline D2 receptor availability was negatively correlated with rates of cocaine self-administration. D2 receptor availability decreased by 15-20% within 1 week of initiating self-administration and remained reduced by approximately 20% during 1 year of exposure. Long-term reductions in D2 receptor availability were observed, with decreases persisting for up to 1 year of abstinence in some monkeys. These data provide evidence for a predisposition to self-administer cocaine based on D2 receptor availability, and demonstrate that the brain dopamine system responds rapidly following cocaine exposure. Individual differences in the rate of recovery of D2 receptor function during abstinence were noted.
Summary: Cerebral muscanmc cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [IIClscopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administra tion and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribu tion kinetics of [llC]scopolamine in normal subjects fol lowing intravenous injection. Scopolamine is initially de livered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accu mulate throughout a 2 h postinjection period in receptor rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [llClscopolamine does Neuropathologic knowledge of many neurologic and psychiatric illnesses is limited to postmortem observations of changes in specific neuronal popu lations or neurochemical markers. These markers
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