Year: 1999
Type: dissertation
Abstract: The behavioural effects of many drugs of abuse increase gradually when they are administered repeatedly, i.e. their behavioural effects are sensitized.Behavioural sensitization can be maintained for months after repeated administration of morphine and other opioids, and it has been associated with drug dependence.The mechanisms involved in the sensitization are not fully clarified.There is evidence of the involvement of cerebral dopaminergic systems in the sensitization to morphine, but participation of neural systems other than the dopaminergic system may also be required in the expression of sensitization.The present series of studies was conducted to study the involvement of cerebral dopaminergic and noradrenergic systems in the behavioural sensitization to morphine in mice.Morphine was given repeatedly to mice for 5 days.After 1, 3 or 5 days' withdrawal, an acute morphine challenge dose was given.The morphine withdrawal and challengeinduced changes in striatal dopamine (DA) metabolism, and in cerebral noradrenaline (NA) metabolism were measured post mortem in tissue samples by high-performance liquid chromatography with electrochemical detection; the morphine-induced changes of locomotor activity were measured as well.Furthermore, the effects of an α2adrenoceptor antagonist, idazoxan, on the morphine-induced changes in striatal DA and cerebral NA metabolism, as well as in locomotor activity, were studied in mice withdrawn for 3 days from the repeated morphine treatment.Acute morphine increased striatal DA turnover and release to a greater extent in mice withdrawn for 3 or 5 days from the repeated morphine treatment than in control mice, while mice were tolerant to the cerebral NA turnover and release increasing effect of acute morphine when withdrawn for 1 or 3 days.At 1-day withdrawal mice were tolerant to the acute morphine-induced locomotor hyperactivity, at 3-day withdrawal the activity was increased similarly as in control mice, but at 5-day withdrawal mice were sensitized to the acute morphine-induced locomotor hyperactivity.Pretreatment
Source: Työväentutkimus Vuosikirja
Author: Juha Airio
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2201820924