NALOXONE-PRECIPITATED CHANGES IN BIOGENIC-AMINES AND THEIR METABOLITES IN VARIOUS BRAIN-REGIONS OF BUTORPHANOL-DEPENDENT RATS

Influence of a naloxone (an opioid receptor antagonist) challenge (5 m g/kg, IP) on levels of biogenic amines and their metabolites in variou s brain regions of rats infused continuously with butorphanol (a mu/de lta/kappa mixed opioid receptor agonist; 26 nmol/mu 1/h) or morphine ( a mu-opioic receptor agonist; 26 nmol/mu 1/h) was investigated using h igh-performance liquid chromatography with electrochemical detection ( HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased th e levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyph enylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-d ependent rats. However, the levels of norepinephrine (NE): serotonin ( 5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdr awal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla . The reduction of 5-HIAA/5-HT ratio was also detected in the limbic a rea. In the animals rendered dependent on morphine, the results obtain ed were similar to those of butorphanol-dependent rats except for chan ges of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction o f DA and its metabolites in specific brain regions (e.g., striatum, li mbic, midbrain, and pons/medulla) play an important role in the expres sion of the opioid withdrawal syndrome.