Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens

The extent to which repeated administration produces tolerance to nicotine-induced increases in dopamine transmission in the nucleus accumbens was investigated in rats. In vivo microdialysis was used to sample extracellular dopamine and metabolites after a nicotine challenge (0.35 mg/kg) in (1) naive rats, (2) acutely pretreated rats (1 prior nicotine injection), and (3) chronically pretreated rats (12-15 prior daily nicotine injections, 0.35 mg/kg per injection). Nicotine increased extracellular DA and its metabolites, and these increases were not significantly altered by either acute or chronic prior exposure to the drug. The failure to find evidence of tolerance is compatible with the hypothesis that the mesolimbic dopaminergic system is a substrate for the reinforcing properties of chronically administered nicotine.     

CT of cochlear otosclerosis (otospongiosis)

High-resolution CT is the method of choice in determining the extent of demineralization in otospongiosis. By comparing the maximum and minimum densities, this examination has become of clinical importance in the diagnostic approach to otosclerosis and in the follow-up of fluorine therapy.     

Dopaminergic regulation of striatal acetylcholine release: importance of D1 and N-methyl-D-aspartate receptors.

The dopaminergic regulation of striatal cholinergic activity was studied using in vivo microdialysis to measure interstitial concentrations of acetylcholine (ACh) and choline in the striata of freely moving rats. The quaternary acetylcholinesterase inhibitor neostigmine (100 nM) was included in the perfusion solution to increase the recovery of ACh. d-Amphetamine (2 mg/kg, s.c.) and nomifensine (5 mg/kg, s.c.) increased the concentration of ACh in the striatal dialysate by 40 to 60%. Interstitial choline concentrations were reduced by both drugs. Administration of the selective D1 receptor antagonist SCH 23390 (0.3 mg/kg, s.c.) decreased the concentration of ACh in the striatal dialysate by 15 to 20%; in contrast, the selective D2 antagonist raclopride (1 mg/kg, s.c.) increased striatal ACh release by 50 to 60%. Raclopride also briefly increased the extracellular concentration of choline. Raclopride blocked the increase in locomotor activity produced by d-amphetamine, but did not further enhance ACh release. In contrast, SCH 23390 completely antagonized the increases in locomotion and striatal ACh release produced by d-amphetamine. These results indicate that d-amphetamine increases ACh release in the striatum via a D1 receptor mechanism. Consistent with this hypothesis, the selective D1 receptor agonist CY 208-243 (1 mg/kg, s.c.) increased striatal ACh release by approximately 60%. In contrast, local application of CY 208-243 (10 microM) and SCH 23390 (10 microM) failed to alter ACh concentrations in the striatal dialysate. Inclusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 microM) in the striatal perfusion solution significantly attenuated the increase in striatal ACh release produced by systemic CY 208-243.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benzodiazepine-induced decreases in extracellular concentrations of dopamine in the nucleus accumbens after acute and repeated administration

In vivo microdialysis was used to assess the effects of acute and repeated injections of the benzodiazepine midazolam on extracellular dopamine (DA) concentrations in the nucleus accumbens. Acute administration of midazolam (5 mg/kg, SC) elicited a 22% decrease in extracellular DA in the nucleus accumbens but failed to affect DA concentrations in the striatum. Similarly, six spaced intravenous infusions of midazolam, at a dose that has previously been found to support self-administration (0.05 mg per infusion), produced a 50% decrease in extracellular DA in the nucleus accumbens. In order to assess the effects of subchronic midazolam injections, two groups of rats were given injections of saline or midazolam (5 mg/kg, SC) for 14 days (two injections per day). A subsequent challenge injection of midazolam (5 mg/kg) decreased extracellular DA in the nucleus accumbens by 25% in both groups, indicating that neither tolerance nor sensitization occurred during the repeated drug administration. These experiments indicate (1) that midazolam differentially affects meso-accumbens and nigrostriatal DA neurons, and (2) that the midazolam-induced decrease in extracellular DA in the nucleus accumbens is not affected by repeated drug administration. The data further suggest that the rewarding effects of midazolam are not associated with increased release of DA in the nucleus accumbens.     

Sexual behavior enhances central dopamine transmission in the male rat

Central dopamine transmission was examined in the nucleus accumbens and striatum of sexually experienced male rats during mating behaviour using in vivo brain microdialysis. Dopamine release increased significantly in the nucleus accumbens when males were placed in a novel mating chamber and when a receptive female was introduced behind a screen partitioning this chamber. Subsequently, during copulation dopamine transmission increased sharply, this being followed by a gradual decrease after the female was removed. In contrast, striatal dopamine transmission increased significantly only during copulation. These data provide a neurochemical basis for the well-known interactions between dopaminergic drugs and male sexual behaviour and demonstrate the feasibility of using brain microdialysis to elucidate the neurochemical correlates of motivated behaviour.     

Cholinergic activity in the rat hippocampus, cortex and striatum correlates with locomotor activity: an in vivo microdialysis study

The possible relationship between behavioral arousal and acetylcholine release in the striatum, hippocampus and frontal cortex was investigated in rats. In vivo microdialysate concentrations of acetylcholine and choline from these brain structures, and photocell beam interruptions (as a measure of behavioral arousal), were measured simultaneously under three conditions: after injections of 1) vehicle or 2) scopolamine (0.4 mg/kg), and 3) before and after the beginning of the rats' night cycle. Dialysate concentrations of ACh in all 3 brain structures and locomotor activity were increased after scopolamine and the onset of the lights out condition. Vehicle injections transiently increased ACh in the hippocampus and cortex and caused short-lasting increases in locomotor activity. Under all conditions, the release of ACh from each of the 3 brain structures correlated with the level of locomotor activity.     

The effect of systemically applied cholinergic drugs on the striatal release of dopamine and its metabolites, as determined by automated brain dialysis in conscious rats

The effects of cholinergic drugs on the in vivo release of dopamine (DA) and its metabolites were studied in the striatum of freely moving rats. The endogenous compounds were sampled by microdialysis and analysed by on-line HPLC. High doses of oxotremorine (5 mumol/kg), physostigmine (3.6 mumol/kg), nicotine (3 mumol/kg) and atropine (10 mumol/kg) were injected i.p. Oxotremorine, physostigmine and atropine failed to modify the release of DA, while nicotine induced a slight (30%) but significant increase in the release of the transmitter. In contrast, oxotremorine and physostigmine did produce a significant rise of the dialysate contents of the DA metabolites. Thus, these data demonstrate clearly that changes in DA metabolism do not necessarily reflect changes in the release of DA. The most interesting findings of the present study is the fact that muscarinic receptor stimulation or blockade does not modify the release of DA from the rat striatum, while nicotine receptor stimulation may exert some stimulatory effect on the release of DA. This conclusion does not support the concept that the mode of action of anticholinergic drugs used in the treatment of parkinsonism, can be ascribed to a modulation of striatal dopaminergic activity.     

Electroconvulsive shock produces large increases in interstitial concentrations of dopamine in the rat striatum: an in vivo microdialysis study.

This study examined the effects of electroconvulsive shock (ECS) on interstitial concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the purine metabolite uric acid, in the striatum using on-line microdialysis in freely moving rats. Interstitial striatal DA increased to 1310% of baseline when the ECS was administered 18 to 24 hours after implantation of the dialysis probe. DOPAC (+ 19%), HVA (+ 30%), 5-HIAA (+10%), and uric acid (+111%) were increased to a smaller extent. The ECS-induced increase in DA was derived from a Ca++ sensitive pool since perfusion of a modified solution in which Ca++ had been replaced with Mg++ blocked this effect.