Biomedical subjects

J L Cornish

Publications and source records attributed to J L Cornish.

12 recordsLinked to original sources

PubMed2001

Repeated cocaine administration into the rat ventral tegmental area produces behavioral sensitization to a systemic cocaine challenge.

The aim of the present study was to investigate the capacity of repeated administration of cocaine (5 nmol/side) or the selective dopamine re-uptake inhibitor GBR 12909 (15 nmol/side) into the ventral tegmental area (VTA) to initiate behavioral sensitization to systemically administered cocaine (15 mg/kg, intraperitoneally). Following 1 week of withdrawal from intra-VTA treatment, cocaine or GBR 12909 pretreated animals displayed sensitized locomotor and rearing behavior to acute systemic cocaine administration. These data support the possibility that increased dopamine transmission in the VTA is involved in the cellular events that determine the initiation of behavioral sensitization to cocaine.

Animals↗

PubMed2001

Cocaine sensitization and craving: differing roles for dopamine and glutamate in the nucleus accumbens.

The repeated administration of cocaine produces enduring neuroadaptations that are associated with enhanced behavioral responsiveness to cocaine administration and lead to cocaine addiction and the manifestation of paranoid psychosis. This review describes the effect of chronic cocaine administration on dopamine and glutamate transmission in the nucleus accumbens, and discusses the relevance of these changes in the initiation of drug craving and relapse to drug abuse. Recent findings suggest that glutamate transmission in the nucleus accumbens is a dominant precipitator of relapse to drug-seeking activity, whereas both dopamine and glutamate transmission are important for sustaining drug-taking behavior.

Adaptation, Physiological↗

PubMed2001

Dopamine-independent locomotion following blockade of N-methyl-D-aspartate receptors in the ventral tegmental area.

Compounds acting in the ventral tegmental area to increase motor activity are thought to do so by activating mesolimbic dopamine transmission. The present report demonstrates that the microinjection of N-methyl-D-aspartate (NMDA) antagonists into the ventral tegmental area produces a dose-dependent increase in motor activity. This effect was not mimicked by antagonizing either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate or metabotropic glutamate receptors in the ventral tegmental area. Three experiments were conducted that indicated that the capacity of NMDA receptor antagonists to elevate motor activity did not involve increased dopamine transmission. 1) The systemic administration of a D1 dopamine receptor antagonist did not inhibit the motor stimulant response to NMDA antagonist injection into the ventral tegmental area except at doses that also inhibited motor activity after an injection of saline into the ventral tegmental area. 2) Stimulating orphanin receptors in the ventral tegmental area selectively inhibits dopamine cells, and this did not alter NMDA antagonist-induced motor activity. Whereas, stimulating gamma-aminobutyric acid (GABA)(B) receptors hyperpolarizes both dopamine and GABA cells in the ventral tegmental area, and this abolished NMDA antagonist-induced motor activity. 3) The microinjection of an NMDA antagonist into the ventral tegmental area did not increase dopamine metabolism in dopamine terminal fields, including the accumbens, striatum, or prefrontal cortex. Also consistent with a lack of dopamine involvement, repeated administration of NMDA antagonist into the ventral tegmental area did not produce behavioral sensitization. These data identify a mechanism to elicit a motor stimulant response from the ventral tegmental area that does not involve activating dopamine transmission.

2-Amino-5-phosphonovalerate↗

PubMed2000

Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction.

Elevated dopamine transmission in the nucleus accumbens is thought to be a primary mediator of addiction to cocaine. However, repeated exposure to cocaine is associated with the recruitment of glutamate transmission. This poses the possibility that the behaviors characterizing cocaine addiction, such as craving-induced relapse, may not be preferentially mediated by dopamine transmission. An animal model of relapse was used to demonstrate that glutamate, and not dopamine transmission in the nucleus accumbens, is a primary mediator of cocaine-induced reinstatement of drug-seeking behavior. Reinstatement was produced by a systemic injection of cocaine or by the microinjection of the glutamate receptor agonist AMPA or dopamine into the nucleus accumbens. It was found that microinjection of an AMPA receptor antagonist into the nucleus accumbens blocked reinstatement by all compounds, whereas a dopamine receptor antagonist was effective only in blocking reinstatement by intra-accumbens dopamine administration. These data suggest an important role for nucleus accumbens glutamate and not dopamine transmission in cocaine-induced relapse to drug-seeking behavior.

Animals↗

PubMed1999

A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior.

This study investigated the effect of ionotropic glutamate receptor agonist or antagonist administration into the nucleus accumbens on the maintenance of cocaine self-administration and the reinstatement of cocaine-seeking behavior. The stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid or N-methyl-D-aspartate glutamate receptors in the nucleus accumbens with either alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid or 1-aminocyclobutane-cis-1,3-dicarboxylic acid, respectively, decreased the number of cocaine-reinforced responses, suggesting an enhancement in the rewarding properties of cocaine. In contrast, blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptors with N-methyl-D-aspartate, or N-methyl-D-aspartate receptors with dizocilpine maleate or 2-amino-5-phosphonovaleric acid had no selective effect on the maintenance of cocaine self-administration. Following one week of extinction from the reinforcing cue of the drug-paired lever, both alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid and 1-aminocyclobutane-cis-1,3-dicarboxylic acid treatment in the nucleus accumbens reinstated cocaine-seeking behavior. However, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid treatment increased responding only on the drug-paired lever, while 1-aminocyclobutane-cis-1,3-dicarboxylic acid increased responding on both the drug-paired and non-drug-paired levers. These results suggest that stimulation of glutamate receptors in the nucleus accumbens augments the reinforcing effect of cocaine, yet glutamate transmission is not required to maintain cocaine self-administration. In addition, increased glutamate transmission in the nucleus accumbens may be involved in facilitating the relapse to cocaine-seeking behavior.

2-Amino-5-phosphonovalerate↗

PubMed1997

A functional interaction between the mesolimbic dopamine system and vasopressin release in the regulation of blood pressure in conscious rats.

The aim of the present study was to further characterize the involvement of the mesolimbic dopamine system in central blood pressure regulation, with particular emphasis on the interaction of this system with the effects of circulating vasopressin. In conscious rats we stimulated the release of endogenous dopamine from mesolimbic/mesocortical terminals by administration of the substance P analogue DiMe-C7 ([pGlu5, MePhe8, Sar9]-Substance P5-11; 10 nmol) into the ventral tegmental area. Chemical stimulation of the ventral tegmental area resulted in a significant increase in blood pressure and heart rate. These effects were prevented by either bilateral electrolytic lesions of the hypothalamic supraoptic nucleus or by systemic pretreatment with the dopamine D2 receptor antagonist raclopride (0.5 mg/kg). Stimulation of the ventral tegmental area also produced a marked increase in the expression of the proto-oncogene c-fos in the supraoptic nucleus and a significant increase in plasma vasopressin levels, suggesting activation of vasopressinergic neurons in this nucleus. However, this effect of stimulation of the ventral tegmental area was not significantly inhibited by pretreatment with raclopride. We suggest that the effects on blood pressure and heart rate of stimulation of the ventral midbrain by micro-injection of DiMe-C7 are the result of combined activation of both dopaminergic and non-dopaminergic cell bodies in this region. Stimulation of non-dopaminergic cells in the ventral midbrain may induce a moderate increase in plasma vasopressin levels by activation of the supraoptic nucleus. An additional stimulation of dopaminergic cells in the ventral midbrain allows the increase in circulating vasopressin levels to become manifest as a pressor response, possibly by inhibition of vasopressin-induced facilitation of baroreflex responses.

Animals↗

PubMed1996

Regional expression of c-fos in rat brain following stimulation of the ventral tegmental area.

This study has investigated the effect of stimulating the region of origin of the mesolimbic dopaminergic system, the ventral tegmental area (VTA), with the substance P analogue DiMe-C7 on the regional expression of c-fos in the rat forebrain. We have previously shown this treatment produced a prolonged increase in blood pressure and heart rate which was mediated by both dopaminergic mechanisms and vasopressin release. Stimulation of the VTA resulted in increased levels of c-Fos immunostaining in several target regions of the mesolimbic dopaminergic system (such as the frontal cortex, olfactory tubercle, islands of Calleja and amygdala), with the notable exception of the nucleus accumbens. A marked increase in c-fos expression was also found in the supraoptic nucleus but not the paraventricular nucleus in the hypothalamus. These results support a role for a number of target areas of the mesolimbic dopaminergic system and vasopressin release in the increase in blood pressure and heart rate produced by stimulation of the VTA.

Animals↗

PubMed1996

Prolonged central effects of quinpirole on cardiovascular regulation.

Central cardiovascular effects of the dopamine D2 receptor agonist quinpirole were studied in conscious rats. The i.v. injection of 0.3 mg/kg of quinpirole in spontaneously hypertensive rats (SHR) caused a rapid but short-lasting increase in blood pressure. Heart rate showed little change. Pretreatment with the centrally acting selective dopamine D2 receptor antagonist raclopride, but not the D1 antagonist SCH23390, completely prevented the rise in blood pressure. A second injection of quinpirole, 30 min after the first injection, induced little change in blood pressure, although at 4 or 24 hr after quinpirole treatment, we observed partial and complete recovery of the pressor response, respectively. This pattern of desensitization was similar to that seen after administration of the dopamine D2 receptor agonists N-propylnorapomorphine (0.3 mg/kg) or quinelorane (0.1 mg/kg), and was similar in spontaneously hypertensive rats, Wistar Kyoto and Sprague-Dawley rats. At 30 min after treatment with quinpirole, the hypotension induced by i.v. injection of clonidine (0.01 mg/kg) or of 8-hydroxy-dipropylaminotetralin (0.1 mg/kg) was markedly reduced when compared to that in saline-pretreated spontaneously hypertensive rats, suggesting a prolonged effect of quinpirole at the level of sympathetic regulation. The rapid fall in blood pressure caused by i.v. injection of the ganglion blocker pentolinium (10 mg/kg) was slightly, but significantly enhanced by treatment with quinpirole, which suggests an overall prolonged increase in resting sympathetic vasomotor tone. This would be difficult to reconcile with an inhibition of the action of sympatholytic drugs, unless it is hypothesized that the increase in sympathetic vasomotor tone was differential between different sympathetic beds or different neuronal populations in the brain. This may prohibit any additional pressor responses and, through a central feedback mechanism, may inhibit the action of sympatholytic drugs. No evidence was found for lasting changes in circulating levels of vasopressin, angiotensin or atrial natriuretic factor, nor were there changes in hematocrit. Cardiac sympathetic tone appeared to be enhanced, although vagal tone was normal and no major changes in baroreflex sensitivity were observed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

Stimulation of the rat mesolimbic dopaminergic system produces a pressor response which is mediated by dopamine D-1 and D-2 receptor activation and the release of vasopressin.

Treatment with dopamine receptor agonists has been shown to induce centrally mediated effects on cardiovascular regulation. We have investigated the effect on blood pressure and heart rate of stimulating the release of endogenous dopamine in the brain from the mesolimbic/mesocortical (A10) dopaminergic system of conscious Sprague-Dawley rats. Stimulation of the region of origin of the A10 dopaminergic system, the ventral tegmental area (VTA), with local micro-injection of the substance P analogue DiMe-C7, produced a dose-dependent increase in blood pressure and heart rate. The injection of 10 nmol of DiMe-C7 produced a maximum increase in blood pressure of 15-20 mmHg at 10 min following administration and a maximum tachycardia of 70-80 B/min. Intravenous pretreatment with the dopamine D-1 receptor antagonist SCH 23390 (0.1 mg/kg) or the dopamine D-2 receptor antagonist raclopride (0.5 mg/kg) markedly inhibited the pressor response and revealed a bradycardia. Furthermore, the pressor response and tachycardia were completely blocked by pretreatment with the vasopressin V-1 receptor antagonist, Pmp1,O-Me-Tyr2-[Arg8]vasopressin (10 micrograms/kg). Pretreatment with the ganglion blocker, pentolinium (10 mg/kg), had little effect on the blood pressure response, however it attenuated the tachycardia. Micro-injection of 10 nmol of DiMe-C7 into a region 2 mm dorsal to the VTA had little effect on blood pressure yet produced a marked bradycardia. The administration of DiMe-C7 into the region of origin of the nigrostriatal A9 dopaminergic system, the substantia nigra, produced a slight but significant increase in blood pressure with little effect on heart rate. Intracerebroventricular administration of DiMe-C7 also produced a pressor response with a more pronounced tachycardia. The blood pressure responses produced by intranigral or i.c.v. injection of DiMe-C7 were not inhibited by pretreating the rats with raclopride. These results suggest an involvement of the mesolimbic A10 dopaminergic system in the regulation of blood pressure and heart rate through the activation of dopamine D-1 and D-2 receptors and vasopressin release.

Animals↗

PubMed1994

Pressor responses to electrical and chemical stimulation of the rat brain A10 dopaminergic system.

Central dopaminergic systems have been implicated in the regulation of blood pressure. We examined the effect on blood pressure of electrical or chemical stimulation of the rat brain ventral tegmental area (VTA) which is the region of origin of the A10 dopaminergic system. Electrical stimulation in urethane-anaesthetised rats (10-120 Hz, 80 microA) produced frequency-dependent increases in blood pressure (max 30-35 mmHg). These pressor responses could be significantly attenuated by pretreatment with the dopamine D2 receptor antagonist haloperidol, but not the D1 receptor antagonist SCH 23390. Chemical stimulation of the VTA, by microinjection of 10 nmol of the substance P analogue DiMe-C7, produced a sustained increase in blood pressure (max 10-15 mmHg), which could be completely prevented by pretreatment with haloperidol. These results suggest that stimulation of dopaminergic neurons in the VTA induces pressor responses and that projections from midbrain dopaminergic neurons, acting on dopamine D2 receptors, play a role in the regulation of blood pressure.

Animals↗

PubMed1992

Color coding patient medications.

"When I first met Mr. K, he had just been discharged from the hospital, where he was treated for congestive heart failure. This was his third admission this year--his physician thought he might not be taking his medications correctly. The doctor had referred him to our home care agency for instructions in taking his medications and for cardiopulmonary assessment." A home care nurse explains how she developed a simple medication coding method to ensure an elderly patient's independence--and health.

Aged↗

PubMedDate not supplied

Inhibition of cardiac baroreflex sensitivity after central dopaminergic stimulation.

1. Stimulation of the mesolimbic dopamine system, by micro-injection of the substance P analogue [pGlu5,MePhe8,Sar9] substance P (DiMe-C7) into the ventral tegmental area induced a prolonged increase in blood pressure and circulating levels of vasopressin. 2. In the present study, this treatment produced a significant decrease of cardiac baroreflex sensitivity in conscious rats. After pretreatment with the dopamine receptor antagonist raclopride, central stimulation failed to produce any changes in baroreflex parameters. 3. The central dopamine-mediated decrease in baroreflex sensitivity may be involved in functionally potentiating the circulatory actions of vasopressin.

Animals↗