Chronic nicotine modifies the effects of morphine on extracellular striatal dopamine and ventral tegmental GABA

Abstract

Previously, we have shown that 7‐week oral nicotine treatment enhances morphine‐induced behaviors and dopaminergic activity in the mouse brain. In this study, we further characterized the nicotine‐morphine interaction in the mesolimbic and nigrostriatal dopaminergic systems, as well as in the GABAergic control of these systems. In nicotine‐pretreated mice, morphine‐induced dopamine release in the caudate putamen and nucleus accumbens was significantly augmented, as measured by microdialysis. Chronic nicotine treatment did not change basal extracellular concentrations of dopamine and its metabolites in the caudate putamen and nucleus accumbens, nor did it affect the rate of dopamine synthesis, as assessed by 3‐hydroxybenzylhydrazine dihydrochloride‐induced DOPA accumulation. GABAergic control of dopaminergic activity was studied by measuring extracellular GABA in the presence of nipecotic acid, an inhibitor of GABA uptake. Acute (0.3 mg/kg or 0.5 mg/kg i.p.) and chronic nicotine, as well as morphine (15 mg/kg s.c.) in control mice decreased nipecotic acid–induced increase in extracellular GABA in the ventral tegmental area/substantia nigra (VTA/SN). In contrast, in nicotine‐treated mice, morphine increased GABA levels in the presence of nipecotic acid. We did not find any alterations in GABAB‐receptor function after chronic nicotine treatment. Thus, our data show that chronic nicotine treatment sensitizes dopaminergic systems to morphine and affects GABAergic systems in the VTA/SN.

High sensitivity HPLC method for analysis of in vivo extracellular GABA using optimized fluorescence parameters for o -phthalaldehyde (OPA)/sulfite derivatives

“…Previous studies using FLD quantified GABA in tissue or brain microdialysates using OPA/thiol derivatives reported ranges of 330–365 nm and 420–530 nm for excitation (λ ex ) and emission (λ em ) wavelengths, respectively [25–28]. Recently, excitation and emission spectra were thoroughly examined for amino acids derivatized with OPA/MPA, including GABA.…”

Interactions between nicotine and drugs of abuse: a review of preclinical findings

“…Intracranial self-stimulation studies (ICSS) in rats show that pretreatment with morphine shifts the ICSS threshold for nicotine down and to the left, suggesting increased efficacy and potency [155]. Nicotine and opiates also produce cross-tolerance [156] or cross-sensitization [157] such that exposure to one drug increases or decreases the response to the other in CPP procedures, depending on the schedule and duration of administration. Further, acute administration of nicotine into the VTA [158], hippocampus [159], or basolateral amygdala [160] potentiates, while mecamylamine inhibits, morphine-induced CPP.…”

Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure

“…S9). Loss of this inhibitory feedback mechanism likely contributes to increased VTA sensitivity to nicotine and other stimuli (23,24), resulting in sensitized DA release in the nucleus accumbens (15) and increased motivation for nicotine intake.…”