Amphetamine actions on pre- and postpubertal rat hippocampal dentate granule neurons (original) (raw)
Related papers
Brain Research, 1995
Repeated intermittent administration of (+)-amphetamine produces sensitisation to many of the behavioural effects of the drug. Evidence suggests that excitatory amino acidergic projections from the prefrontal cortex (PFC) to dopaminergic (DA) neurons in the ventral midbrain may be partly involved in the maintenance of sensitisation once induced. The present study was designed to investigate whether chronic amphetamine administration produces any alteration to this input, by assessing the impact of single pulse electrical stimulation of the PFC (0.25 and 0.5 mA) on the extracellular activity of individual midbrain DA neurons in drug and vehicle treated rats. Animals were administered amphetamine according to a schedule known to produce sensitisation (2.5 mg/kg free base, once daily for 6 days; s.c.), and the effect of PFC stimulation was assessed on withdrawal days 2 and 10. In addition to single spike firing patterns, the ability of the stimulation to elicit stimulus bound (time-locked) burst events was also noted. In the majority of cases, the elicited responses could be broadly categorised into two types --ones characterised by an initial excitation (E responses) and ones characterised by excitiation following an initial inhibition (IE responses). On withdrawal day 2, IE responses were affected such that, in those responses which contained time-locked bursts in their excitatory phases, the stimulus produced a time-locked burst on a greater percentage of trials. On withdrawal day 10, the principal change was that E responses were more likely to occur in amphetamine-treated animals than controls (0.25 mA; 57.1% vs. 41.2% of responses, respectively; 0.5 mA; 36.7% vs. 23.5% of responses, respectively). It is argued that an increase in the proportion of excitatory responses in drug animals indicates a potentiation of the excitatory drive to the DA neurons. Insofar as sensitisation in the longer term relies upon an enhancement of amphetamine-induced dopamine release in the forebrain, this may be one mechanism by which it is achieved.
Brain Research, 1996
To investigate neural mechanisms associated with behavioral sensitization to amphetamine, we studied the effect of an intrastriatal infusion of amphetamine on nigrostriatal axon terminal electrical excitability in rats following withdrawal from repeated systemic treatment. Rats were injected with amphetamine 2.5 mg/kg S.C. or saline daily for 4 days, Either 24 h or 14 days after the last injection, extracellular recordings were obtained from dopaminergic neurons of the substantia nigra, in a blind design in which the experimenter did not know the pretreatment regime. In order to assess the electrical excitability of the nigrostriatal axonal field, neurons were activated antidromically by stimulating their terminal fields in the striatum. As previously reported, striatal infusion of amphetamine (1 kM/0.3 ~1) in control animals resulted in a significant reduction in excitability as indicated by an increase in striatal stimulus current necessary to evoke antidromic activity. In contrast. intrastriatal amphetamine administration to amphetamine-pretreated animals did not decrease excitability. Spontaneous firing rates and patterns of cell discharge did not differ between saline-and amphetamine-treated animals. The chronic amphetamine-induced change in the effect of an acute intrastriatal amphetamine infusion on nigrostriatal terminal excitability may be due to enduring alterations in the amphetamine-induced release of dopamine and other striatal neurotransmitters or to changes in the sensitivity of presynaptic hetero-and/or autoreceptors on the dopaminergic axons.
Brain Research, 2001
The purpose of this study was to examine the influence of chronic d-amphetamine (AMPH) treatment (2 mg / kg i.p., for 9 consecutive days) on behavioral and neurochemical responses to a subsequent exposure -4 days after the last AMPH injection -to the elevated plus-maze (EPM), as well as to determine the involvement of a dopaminergic mechanism in that influence. Results showed that chronic AMPH treatment induced an 'anxiogenic-like' response when animals were evaluated in the EPM test. Pretreatment with either haloperidol (HAL, 1 mg / kg i.p., 20 min prior to each injection) or SCH-23390 (0.1 mg / kg i.p., 10 min prior to each injection) completely abolished the chronic AMPH-induced 'anxiogenic-like' effect displayed in the EPM test. However, sulpiride pretreatment (60 mg / kg i.p., 10 min prior to each AMPH injection) did not modify such effect. In addition, rats treated with AMPH and subsequently exposed to the EPM, showed a decrease in the maximal GABA-stimulated chloride uptake in cortical microsacs. HAL pretreatment restored the maximal chloride uptake induced by chronic AMPH. Altogether, these results suggest that: (1) previous exposure to chronic AMPH treatment induces an increased emotional response following a conflict situation, (2) dopamine D receptors are mainly involved in chronic 1 AMPH-induced changes in the behavior displayed in EPM test, and (3) an interaction between GABAergic and dopaminergic mechanisms may be implicated in neurochemical and behavioral changes induced by chronic AMPH treatment.
Effects of Acute and Chronic Amphetamine Intoxication on Brain Catecholamines in the Guinea Pig*
Acta Pharmacologica et Toxicologica, 1971
A bstract: The effects of amphetamine on central and peripheral catecholamines have been studied in guinea pigs, since in this species, unlike several others, amphetamine is not metabolized by p-hydroxylation. Twenty mg/kg of dl-amphetamine-sulphate given intraperitoneally caused a 40 % decrease in brain and heart noradrenaline, a 13 % decrease in brain dopamine and a 60 % decrease in homovanillic acid in the caudate nucleus, four hours after its administration. The changes in tissue catecholamine levels and the increase in motor activity followed the time-course of the amphetamine concentrations both in the brain and plasma. After chronic administration of amphetamine at 12 hourly intervals for 7 or 18 days, there was a further decrease in brain and heart catecholamine and homovanillic acid levels. A 4-fold increase in the 3-0-methylated metabolites of noradrenaline and dopamine in brain after the administration of amphetamine to guinea pigs pretreated with nialamide and an increase in the urinary excretion of NA (13-fold) and adrenaline (3-fold) provided evidence for an amphetamine induced release of central and peripheral catecholamines as has previously been reported in rats and cats. Amphetamine disappeared from brain and plasma with an apparent half-life of 2.5-3.1 hours. Only amphetamine and hippuric acid were recovered in the urine after the administration of radioactively labelled amphetamine. No p-or (3-hydroxylated metabolites of amphetamine were present in the brain or heart tissues in the guinea pig. The results show that acute and chronic amphetamine administration cauSes changes in endogenous catecholamines in guinea-pigs similar to those found previously in rats in spite of differences in the metabolism of amphetamine between the two species.
Pharmacology Biochemistry and Behavior, 1992
Sensitization and individual differences to IP amphetamine, cocaine, or caffeine following repeated intracranial amphetamine infusions. PHARMACOL BIOCHEM BEHAV 43(3) [815][816][817][818][819][820][821][822][823] 1992.-Rats that have a high locomotor response to novelty (HR) sensitize more readily to IPadministered amphetamine than rats with a low locomotor response (LR) to novelty. This experiment compared sensitization in HR and LR rats following amphetamine (3.0/~g/side for 5 days) infused bilaterally into either the nucleus accumbens (NACC), ventral tegmental area (VTA), or the medial frontal cortex (MFC). The subsequent locomotor response to IPadministered d-amphetamine sulfate (1 mg/kg), cocaine HCI (15 mg/kg), and caffeine benzoate (20 mg/kg) was also examined. No differences were observed between HR and LR rats following amphetamine infusion into either the MFC, NACC, or VTA. However, HR rats showed greater locomotor activity compared to LR rats following either IP amphetamine, cocaine, or caffeine for subjects cannulated in the NACC, MFC, or the VTA. Repeated infusions of amphetamine into the VTA increased the locomotor response to both IP amphetamine and cocaine, but not to IP caffeine, while repeated infusions of amphetamine into the NACC or MFC had no effect on locomotor response to any drug subsequently administered IP. The results support previous findings that changes induced by intra-VTA infusions, but not intra-NACC or MFC infusions, of amphetamine induce sensitization to IP-administered amphetamine and cocaine. Findings from the present experiment indicate the ability of the dopamine cell body region, but not the dopamine terminal fields, to produce locomotor sensitization to amphetamine and cocaine. The results from the present experiment also indicate the lack of localization to one of studied regions of individual differences. Further, it appears that more than dopamine is involved because both dopaminergicdependent and -independent stimulant drugs produce individual differences.
Intracerebral self-administration of amphetamine by rhesus monkeys
Neuroscience Letters, 1981
Four rhesus monkeys received intracranial implantation of cannulae aimed at the orbitofrontal cortex. Electrical intracranial self-stimulation was obtained readily from insulated electrodes placed temporarily into the orbitofrontal cortex via the outer guide tubes. Subsequently, each subject acquired a panel press operant response to deliver 0.05 #l of D-amphetamine (10 6 M) into the orbitofrontal cortex via an inner cannula. The rate of panel pressing increased over several daily test sessions and extinguished after substitution of the vehicle solution. One animal responded readily on a fixed ratio-10 schedule. Control injections into the nucleus accumbens and lateral ventricles failed to maintain self-administration behavior.