Involvement of brain biogenic amines in the electroencephalographic and behavioural effects of morphine in post-addict rats

Abstract

Rats were prepared with chronic cortical and temporalis muscle electrodes for recording of the electroencephalogram (EEG) and electromyogram and with chronic indwelling intravenous cannulae for drug administration. To induce dependence on morphine, progressively increasing intravenous doses were delivered automatically over a period of 6–7 days, after which time the injections were discontinued. Administration of morphine (10mg/kg, i.p.) to post-addict rats abstinent for 7 days was followed by the immediate appearance of EEG desynchronization and marked behavioural hyperarousal. After pretreatment of rats with (±) α-methyl-para-tyrosine (α-MPT), para-chlorophenylalanine ( p-CPA), or a combination of α-MPT and p-CPA during the period of morphine addiction and withdrawal, these EEG and behavioural effects of morphine, given on the eighth day of abstinence, were unaltered. Brain levels of the catecholamines norepinephrine (NE) and dopamine (DA) measured in un-treated post-addict rats after a morphine test dose (10mg/kg, i.p.) likewise remained unchanged. Brain levels of serotonin (5-HT), determined 30 min after the morphine challenge, were significantly elevated. Determinations of brain NE and DA levels, made 30 min after injection of morphine to postaddict rats pretreated 4 hr earlier with a-MPT, showed a reduction in brain DA utilization. These results suggest that both dopaminergic and serotonergic brain pathways may be involved in the mediation of EEG and behavioural responses to morphine in post-addict rats.