5-HT, dopamine, norepinephrine, and related metabolites in brain of low alcohol drinking (LAD) rats shift after chronic intra-hippocampal infusion of harman

Abstract

Harman (1-methyl-beta-carboline) has been shown to induce preference for alcohol in the genetically bred, low alcohol drinking (LAD) rat. This study was undertaken in the LAD rat to determine whether monoamines and their metabolites in different regions of the brain are altered by harman infused chronically into the dorsal hippocampus. For this purpose, a cannula was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously within the intrascapular space. The pump was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman, which was delivered at a rate of 1.0 or 3.0 micrograms/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, a standard preference test for ethyl alcohol was given to the rats over 10 days in which concentrations were increased daily from 3%-30%. The higher concentration of harman infused into the hippocampus elevated the level of serotonin (5-HT), both ipsilateral and contralateral to the hippocampal site of infusion, as well as in the midbrain, frontal cortex, striatum and nucleus accumbens. Similarly, this treatment resulted in a rise in the levels of norepinephrine in the hippocampus and midbrain but decreases in dopamine levels in the pons. The levels of 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were diminished in the pons of rats given 3.0 micrograms/h harman, whereas both concentrations of the beta-carboline reduced the level of homovanillic acid (HVA) in the frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Harmane on the Convulsive Threshold in Epilepsy Models in Mice

“…A further explanation for the effects of harmane may involve changes in dopamine and serotonin levels. It has been shown that harmane increases extracellular dopamine and serotonin levels, probably by inhibition of monoamine oxidase A 11. It has also been shown that high doses of harmane increase both homovanillic acid and 5‐hydroxyindole acetic acid levels 11,18.…”

“…Harmane is a competitive inhibitor of benzodiazepine receptor binding in vitro 8. A variety of other biochemical properties have also been described for β‐carbolines, including inhibition of monoamine oxidase A, competitive inhibition of serotonin uptake, general inhibition of sodium‐dependent transport, binding to opiate receptors, and probable action on dopamine receptors 9–11. Recently it has also been shown that harmane is an endogenous ligand of imidazoline receptors 12…”

Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol

“…Co-administration THP and tryptoline resulted in a synergistic increase in EtOH preference and consumption (Myers and Oblinger, 1977). Hippocampal microinjections of TBCs produced alterations in both 5-HT and norepinephrine levels thereby significantly augmenting EtOH preference and consumption in low alcohol drinking (LAD) rats (Huttunen and Myers, 1987; Adell and Myers, 1995). Additionally, TBCs have been shown to possess an affinity for the delta opioid receptor (Airaksinen et al, 1984).…”

What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

“…Co-infusion of tryptoline and THP augmented alcohol preference and consumption in a synergistic nature (Myers & Oblinger, 1977). Infusion of TBC into the hippocampus of low alcohol drinking (LAD) rats increased alcohol preference and consumption (Adell & Myers, 1995; Huttunen & Myers, 1987) through increases in both 5-HT and norepinephrine levels (Adell & Myers, 1995). TBCs exhibit an affinity for the δ opioid receptor (DOR) (Airaksinen et al, 1984), but the pharmacological properties of TBCs have not been fully examined.…”