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Cyclo(Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine: agonist binding to D2 dopamine receptors correlates with stereotypic behavior.

We have previously shown that MIF and its structural analog, cyclo-(Leu-Gly), block analgesic tolerance and some signs of physical dependence following chronic opiate administration. The mechanism of action of these peptides has not been clearly elucidated. The data presented here suggests that chronic opiate administration causes a behavioral supersensitivity to dopamine (DA) agonists which is highly correlated with an increase in D2-Hi receptor affinity for DA agonists, but not antagonists. Both the behavioral and receptor changes are blocked by prior administration of cyclo(Leu-Gly). This suggests that the ability of cyclo(Leu-Gly) to block the development of opiate addictive states may involve DA synaptic elements.

Animals↗

Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain?

The possibility that REM sleep deprivation induces increased sensitivity of rats to the effects of apomorphine was investigated. Rats were deprived of REM sleep by placing them on 6.0 cm platforms for 3 days. Stress control groups consisting of rats placed on 14 cm platforms (control rats) and groups of nonmanipulated animals (normal rats) were used for comparison purposes. Several doses of apomorphine were administered to these 3 groups of animals, and aggressive behavior, stereotyped behavior, verticalization and body temperature were recorded. All measures indicated that REM-deprived rats were more responsive to apomorphine than the normal and control animals, with the exception of verticalization effect, in which both REM-deprived and control animals reacted similarly. These results suggest that REM deprivation induced supersensitivity in brain dopamine receptors. Other possible interpretations are also discussed.

Aggression↗

The Stereotypy Rating Inventory for frontotemporal lobar degeneration.

A many behavioral disturbances, Stereotypic behaviors are among the best discriminators of Frontotemporal Lobar Degeneration (FTLD). A recent preliminary report suggests many of the behavioral symptoms, including stereotypic behaviors in FTLD patients, respond to medication with selective serotonin re-uptake inhibitors. However, there is no scale that evaluates stereotypic behaviors comprehensively. To assess the wide range of stereotypic behaviors encountered in FTLD, we developed a new instrument, the Stereotypy Rating Inventory (SRI). The SRI assesses five distinctive stereotypic behavioral disturbances often seen in patients with FTLD: eating and cooking behaviors, roaming, speaking, movements, and daily rhythm. The SRI uses the same technique as the Neuropsychiatric Inventory (NPI) in that both the frequency and the severity of each behavior are determined. The studies reported here demonstrate the content and concurrent validity, as well as inter-rater and test-retest reliability, of the instrument. Scores of FTLD patients (n=26) on the SRI were much higher than those of patients with Alzheimer's disease (n=46), patients with vascular dementia (n=26), and normal control subjects (n=40). The SRI appears to be a useful instrument for detecting stereotypic behaviors and monitoring of therapies in FTLD patients.

Aged↗