Dopamine efflux studies into in vivo actions of psychostimulant drugs.
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Benzazepines↗
Biomedical subjects
T Guix
Publications and source records attributed to T Guix.
Amphetamine enhances extracellular concentrations of dopamine and acetylcholine in dorsolateral striatum and nucleus accumbens of freely moving rats.
The effect of two consecutive administrations of amphetamine (1.5 mg/kg, s.c.; 2 h apart) on dopamine (DA) and acetylcholine (ACh) efflux in dorsolateral striatum and nucleus accumbens was studied with in vivo microdialysis in freely moving rats. Amphetamine was found to cause a more persistent increase of extracellular DA in the dorsolateral striatum than in the nucleus accumbens. The increase in DA overflow by amphetamine was accompanied by an increase of extracellular ACh in both brain areas. The results are inconsistent with the hypothesis of an amphetamine-induced inhibitory regulation by DA on ACh overflow.
Acetylcholine↗
High-performance liquid chromatographic separation of caffeine, theophylline, theobromine and paraxanthine in rat brain and serum.
Caffeine and its metabolites theophylline, theobromine and paraxanthine have been determined in rat brain and serum samples by high-performance liquid chromatography with ultraviolet detection. The recovery, 85-103%, allowed quantification by external standard methods. The variability was found to be less than 3 and 7% for intra-day and inter-day assays, respectively. The detection limit, 1.57 ng of methylxanthines on column, allowed the determination of 62.5 ng/g or ml in biological material. Rats treated with 30 mg/kg caffeine (subcutaneously) were sacrificed at different times (1, 6, 12 and 24 h). Higher concentrations of methylxanthines (specially paraxanthine) were observed in the striatum than in the rest of the brain, and it was also observed that the clearance of methylxanthines was faster in serum than in brain structures.
Animals↗
Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes.
We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine.
Animals↗
T-maze performance in rats following chronic neuroleptic treatment.
The effects of chronic haloperidol treatment (0.5 mg/kg/day for 21 days) on maze learning in the rat were studied. There were no differences between haloperidol- and saline-treated groups in percentage of correct responses, but the latency to respond was longer and extinction was faster in the haloperidol-treated group. We speculated that differences between both groups were due to a decrease of appetitive motivation in haloperidol-treated animals, probably caused by a decrease of dopaminergic neurotransmission.
Animals↗
Is experimental catalepsy properly measured?
Following logarithmic transformation (ln) of total duration of haloperidol-induced catalepsy in the rat, measured by means of the bar test, a normalization of the results is achieved. With the help of this transformation we have been able to study what are probably the most important variables involved in the measuring of experimental catalepsy and to establish some criteria for a better use of such measures: 1) repeated measures of catalepsy have to be taken in order to avoid the stress-induced inhibition of catalepsy caused by the new experimental situation, 2) the dose of neuroleptic used has to be sufficiently low to permit the measurement of total or real duration of catalepsy between two determinations, and 3) the dose of neuroleptic has to be sufficiently high to prevent the development of a learned "pseudocatalepsy."
Adrenal Glands↗
BHT-920 and LY-171555 (quinpirole) have similar affinities for striatal D-2 dopamine receptors, and similar affinities for striatal D-1 dopamine receptors.
The affinity of LY-171555 (quinpirole) and BHT-920 for both states of rat striatal dopamine D-1 and D-2 receptors was determined. Although these drugs have different pharmacological effects in experimental animals, we found that they had similar affinities for both D-1 and D-2 receptors.
Animals↗
Theophylline reverses haloperidol-induced catalepsy in the rat. Possible relevance to the pharmacological treatment of psychosis.
The effect of theophylline (5, 15, or 30 mg/kg sc) on the catalepsy induced by haloperidol in the rat was studied. Theophylline was shown to induce a dose-dependent inhibition of this catalepsy. These data support the hypothesis that the methylxanthines are dopamine agonists and suggest that coffee, tea, and cola drinks should be avoided by patients undergoing neuroleptic treatment.
Animals↗
Conditioning of rotational behavior after the administration of a single dose of apomorphine in rats with unilateral denervation of the dopaminergic nigrostriatal pathway: relevance to drug addiction.
Our aim is to study the relationship of drug activation of the dopamine neurotransmission system and the conditioning of environmental stimuli present at the time of drug administration. We injected a single dose of apomorphine (0.05 mg/kg SC) in rats with the nigrostriatal dopamine pathways unilaterally denervated with 6-hydroxydopamine, which generates rotational behavior contralateral to the lesioned hemisphere. We observed rotational behavior without apomorphine administration when animals were reexposed at different time intervals to the same environment in which they performed turning behavior. The present findings show that this rotational behavior can be conditioned to environmental stimuli in a strong and long-lasting way. In light of the relationship between opioids and the dopaminergic system, similar conditioning could take place in the learning processes implicated in drug addiction.
Animals↗