PubMed Health⌕ Search

Biomedical subjects

D B Neill

Publications and source records attributed to D B Neill.

At least 19 recordsLinked to original sources
PubMed1992

6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence cocaine-induced place conditioning.

This study investigated the involvement of medial prefrontal cortex (mPFC) dopamine in cocaine place conditioning using a totally balanced place conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These lesions significantly depleted dopamine (-83%) and norepinephrine (-70%) in the mPFC but there were no significant reductions in either the nucleus accumbens or in the caudate-putamen compared with sham-operated controls. Furthermore, serotonin levels were not affected in any of the brain regions investigated. These lesions failed to attenuate place conditioning induced by the intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham lesioned controls. In addition, there were no significant differences in spontaneous locomotor activity between the two groups during the preconditioning phase or the test phase. These results suggest that 6-OHDA lesions which produced profound depletions of dopamine and norepinephrine in the mPFC did not alter the rewarding efficacy of cocaine as measured by the place conditioning paradigm.

Animals↗
PubMed1992

Conditioned locomotor activity but not conditioned place preference following intra-accumbens infusions of cocaine.

In the first experiment, the conditioned place preference (CPP) paradigm was used to examine the rewarding properties of bilateral microinfusions of cocaine HCl into the nucleus accumbens (0, 12.5, 25, 50, or 100 micrograms). No dose of intra-accumbens cocaine induced a significant CPP. However, bilateral intra-accumbens infusions of d-amphetamine sulfate (10 micrograms) or intraperitoneal administration of cocaine HCl (5 or 10 mg/kg) both produced a significant preference for the drug-paired compartment. In the second experiment, the ability of bilateral intra-accumbens infusions of cocaine HCl (50 micrograms) to elicit conditioned locomotor activity (CLA) was examined. During the conditioning trials, intra-accumbens cocaine significantly increased locomotor activity. On the test day, when no drug was administered, the group that had previously received cocaine in the activity chamber showed significantly greater locomotor activity than the vehicle control group. This demonstration of CLA indicates that rats are able to associate the effects of intra-accumbens infusions of cocaine with environmental stimuli; however, these infusions are not rewarding as measured by the CPP paradigm. In addition, these results may indicate important differences between the neural substrates for cocaine and amphetamine reward and reveal a dissociation between CPP and CLA.

Amphetamine↗
PubMed1992

Individual differences in amphetamine sensitization: dose-dependent effects.

Rats were screened for locomotor activity in a novel environment and divided into high (HR) or low (LR) responders based on whether their locomotor score for the first hour was above or below the median. In the first experiment, HR and LR rats were compared for their locomotor response following repeated administration of either 0.0, 0.5, 1.0, or 1.5 mg/kg d-amphetamine sulfate (AMPH). Injections of either 0.5 or 1.0 mg/kg AMPH produced higher locomotor activity in HR rats than in LR rats. Furthermore, there was a correlation between the locomotor response to novelty and the response to either 0.5 or 1.0 mg/kg AMPH. In addition, whereas both groups of rats developed the same degree of sensitization to 0.5 mg/kg AMPH, only the HR rats developed pronounced sensitization to repeated administration of 1.0 mg/kg AMPH. When both HR and LR were considered, there was a significant correlation between response to novelty and the extent of sensitization to the locomotor-stimulating properties of 1.0 mg/kg AMPH. There were no differences in locomotor activity or sensitization between HR and LR rats following the highest dose of AMPH (1.5 mg/kg). In a separate experiment, HR and LR rats were compared for locomotor activity following a series of intracranial infusions of AMPH. There were no overall differences in locomotor activity between the HR and LR groups following AMPH infusions into either the nucleus accumbens (NACC) or the anterior dorsal striatum (ADS). However, the locomotor activity scores in the novel environment significantly correlated with the locomotor response to 3.0 micrograms AMPH infused into either the NACC or ADS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1991

Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine.

The relationship between a rat's locomotor response to a novel environment and its behavioral and dopaminergic responses to cocaine was examined. Subjects were divided into two groups based on their locomotor response to a novel environment. Subjects who had a novelty response above the median were classified as high responders (HR), while those with a novelty response below the median were classified as low responders (LR). Following administration of cocaine-HCl (0, 2.5, 5.0, 10.0, or 15.0 mg/kg), HR rats showed a greater locomotor response than LR rats. Moreover, there was a significant correlation between a subject's locomotor response to the novel environment and the locomotor response to either 10.0 (r = 0.65) or 15.0 (r = 0.92) mg/kg cocaine. In a separate experiment, the extracellular concentration of dopamine in the nucleus accumbens (NACC) was monitored using microdialysis procedures. Following cocaine administration (15.0 mg/kg) HR rats showed a larger NACC dopamine response and greater locomotor activity than LR rats. In addition, there was a threefold greater locomotor activity to dopamine ratio in HR rats than in LR rats. A correlation between a subject's locomotor response to a novel environment and the dopaminergic response to cocaine was also evident. These results suggest that differences in the locomotor response to cocaine can, to some degree, be predicted by a rat's locomotor response to a novel environment, and that variations in dopamine-dependent mechanisms of the NACC may underlie these individual differences.

Animals↗
PubMed1991

Individual differences in locomotor activity and sensitization.

Male rats were screened for locomotor activity in a novel environment and divided into high (HR) and low (LR) responders based on whether their locomotor activity score for the first hour was above or below the median locomotor activity for the subject sample. Subsequently, the locomotor response to repeated administration of either amphetamine (AMPH; 0.5 mg/kg), cocaine (10 mg/kg), scopolamine (0.5 mg/kg) or saline was monitored in separate groups of HR and LR rats. HR rats had significantly higher overall activity scores than LR rats for all 3 drugs. Both HR and LR rats developed tolerance at the same rate to repeated scopolamine administration. In contrast, only HR rats showed pronounced sensitization to the locomotor stimulating properties of AMPH and a direct correlation was evident between the locomotor response to novelty and the magnitude of sensitization. These results suggest that an individual's response to a novel environment can, to a certain extent, predict drug-induced locomotor activity and that individual differences in the response to novelty and sensitization to AMPH may result from individual variations in a common neural mechanism.

Amphetamine↗
PubMed1988

Dopamine release at behaviorally relevant parameters of nigrostriatal stimulation: effects of current and frequency.

Released dopamine was monitored voltammetrically in the rat striatum in response to electrical stimulation of the nigrostriatal bundle. Stimulation parameters encompassed those typically used in behavioral studies. Dopamine released during intracranial self-stimulation (ICSS)-like stimulation reached a maximum within the first minute of stimulation, then rapidly decreased. The pattern of release obtained with continuous stimulation as a function of current and frequency supports the view that as the stimulation current is increased, a greater number of neurons are stimulated, while increasing the frequency of stimulation results in a fixed population of neurons being stimulated more intensely. Computer modeling of stimulated release from a population of dopaminergic nerve terminals was used to interpret effects of current and frequency and to predict ICSS release patterns as a function of schedule of reinforcement.

Animals↗
PubMed1988

Caffeine elevates reinforcement threshold for electrical brain stimulation: tolerance and withdrawal changes.

Caffeine dose-dependently increased the reinforcement threshold for electrical self-stimulation of the brain in rats, which is opposite to the effect of other behavioral stimulants. Tolerance to this effect of caffeine developed rapidly with daily drug administration. Abrupt cessation of daily drug treatment was followed by decreases in reinforcement threshold and response rate lasting 24-48 h, changes consistent with a drug withdrawal phenomenon. Because caffeine has the characteristics of a drug of abuse, these results question the generality of hypotheses relating the abuse potential of a drug to its ability to sensitize brain reward systems.

Animals↗
PubMed1987

Detecting behaviorally relevant changes in extracellular dopamine with microdialysis.

A method is described for monitoring extracellular levels of striatal dopamine in the rat during behavior. The extracellular fluid is sampled using a microdialysis probe modified for use in behaving animals. Dopamine concentration in the perfusate is determined every 5 min using an automated smallbore chromatographic system with electrochemical detection. The system is capable of detecting behaviorally related changes of 5 nM, in extracellular dopamine.

Animals↗
PubMed1986

Striatal dopamine activity and unilateral barpressing in rats.

A micro-punch tissue assay was used to measure changes in dopamine content at twenty-six sites within the striatum of rats trained to barpress exclusively with one forepaw for food pellets. Analysis of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was carried out using HPLC with electrochemical detection. The barpress group had a significantly higher DOPAC/DA ratio in both the contralateral and ipsilateral hemispheres when compared to feeding and homecage controls. The DOPAC/DA ratio is considered to be a measure of dopaminergic neuronal activity, thus suggesting a bilateral activation of the neostriatal dopaminergic afferents as a result of the motor performance. Topographical analysis within the barpress group revealed an anterior-posterior, medial-lateral gradient of dopaminergic activity with the posterior and lateral sites showing the greatest increases over the controls. The results of this experiment indicate that localized changes in neuronal activity can be monitored with the micro-punch assay-HPLC/EC technique and that voluntary motor behavior produces an activation of the striatal dopamine system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat.

Unilateral 6-hydroxydopamine injections into the lateral neostriatum disrupted the ability of rats to retrieve small food pellets with the contralateral forepaw. Similar injections into the medial striatum did not interfere with performance accuracy. Dopamine assays indicated that of the 5 striatal subregions analyzed, the lateral striatum at the level of the anterior commissure was most directly related to the behavioral deficit. The behavioral results are interpreted as providing evidence in support of a sensory role for the lateral striatal dopamine system.

Animals↗
PubMed1985

In vivo voltammetric determination of the kinetics of dopamine metabolism in the rat.

In vivo voltammetry at carbon paste electrodes placed in the striatum of chloral hydrate-anesthetized rats was used to monitor changes in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) following 1-min periods of electrical stimulation of the ascending nigro-striatal pathways. Statistical analysis of resultant changes in DOPAC allows simultaneous determination of the rate constants for the turnover of both dopamine (DA) (0.046/min) and DOPAC (0.053/min.). The data demonstrate that there are substantial temporal differences between neuronal release of DA and changes in striatal DOPAC levels. This should be considered when metabolite measurements are used as an index of neurotransmitter activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Identification of a subregion within rat neostriatum for the dopaminergic modulation of lateral hypothalamic self-stimulation.

Experiments were conducted to test the hypothesis that the involvement of neostriatal dopaminergic transmission in lateral hypothalamic self-stimulation might be specific to a striatal subregion. Crystalline application of dopamine or D-amphetamine increased self-stimulation rate only when made to ventral anterior striatum (VAS); more dorsal or posterior applications were ineffective. A comparison of dose-response functions for dopamine using solution injections in VAS and posterior striatum (PS) confirmed that only VAS was responsive. Injections or applications of 6-hydroxydopamine suppressed responding only when made into VAS. Haloperidol injections decreased responding only for VAS and not PS injection sites. Applications or injections of scopolamine often increased responding when made into VAS, but this effect was unreliable. Applications or injections of scopolamine to more posterior sites consistently suppressed responding. It was concluded that dopaminergic transmission in VAS, alone among the striatal sites tested, is facilitatory on hypothalamic self-stimulation. The effects of drug applications to nucleus accumbens were generally similar to VAS, and it was suggested that these areas may be functionally similar. An examination of the known afferents to VAS indicated that this area of neostriatum, like n. accumbens, may be influenced by activity in limbic structures. This anatomy may help provide an understanding of how neostriatum, traditionally considered to have a motor function, might be involved in central reward processes.

Animals↗
PubMed1978

Anatomical specificity within rat striatum for the dopaminergic modulation of DRL responding and activity.

The direct application of microgram quantities of crystalline dopamine, D-amphetamine, or scopolamine to the ventral anterior region of the neostriatum of rats decreased response efficiency on a 'differential reinforcement of low rate' 10 sec schedule of reinforcement. Similar applications to the dorsal globus pallidus or posterior striatum either did not alter or increased response efficiency. A comparison of dose-response functions for injections of dopamine in solution into ventral anterior, central and posterior striatum confirmed that only injections into ventral anterior striatum (VAS) decreased response efficiency on the DRL schedule. The same striatal map was found for the dopamine-induced increase in spontaneous locomotor activity in tilt boxes. It was concluded that dopaminergic transmission in ventral anterior striatum, in contrast to the other striatal and pallidal sites tested, is involved in the modulation of behavioral arousal.

Animals↗
PubMed1976

Frontal-striatal control of behavioral inhibition in the rat.

The direct application of crystalline dopamine, D-amphetamine or scopolamine in microgram quantities to the ventral anterior region of the corpus striatum (VAS) of rats increased their responding for food on a modified DRL-30 sec schedule of reinforcement. Similar applications of norepinephrine were less effective than dopamine, while the anticholinesterase eserine depressed responding. Electrolytic lesions of the ventrolateral, but not the dorsomedial, prefrontal cortex of rats also increased their response rates. These results were interpreted as being consistent with the idea of a dopamine-acetylcholine antagonism in the VAS whose net output modulate behavioral inhibition. This striatal mechanism may be influenced by the ventrolateral prefrontal cortex.

Animals↗