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M A Bozarth

Publications and source records attributed to M A Bozarth.

36 records · Page 2Linked to original sources
PubMed1985

Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat.

Laboratory rats were given unlimited access to intravenous cocaine hydrochloride or heroin hydrochloride. Animals self-administering cocaine quickly developed a pattern of episodic drug intake, with periods of excessive cocaine self-administration alternating with brief periods of abstinence. Subjects allowed continuous access to intravenous heroin showed stable drug self-administration, with a gradual increase in daily heroin intake over the first two weeks of testing. The general health of the animals became markedly different: those self-administering heroin maintained grooming behavior, pretesting body weight, and a good state of general health; rats self-administering cocaine tended to cease grooming behavior, to lose up to 47% of their pretesting body weight, and to show a pronounced deterioration in general health. The mortality rate for 30 days of continuous testing was 36% for animals self-administering heroin and 90% for those self-administering cocaine. These results suggest that cocaine is a much more toxic compound than heroin when animals are given unlimited access to intravenous drug.

Animals↗
PubMed1985

Concurrent heroin self-administration and intracranial self-stimulation in rats.

In a two-lever testing chamber, rats lever pressed for lateral hypothalamic brain stimulation or intravenous heroin reinforcers on a concurrent FR1 FR1 schedule of reinforcement. Responding for stimulation did not alter the rate of heroin self-administration, and responding for heroin caused increased responding for stimulation. Discontinuing heroin injections, or administering 3 mg/kg of naloxone, disrupted responding for both reinforcers, while changing the unit dose of heroin did not appreciably affect response rates for stimulation. This experiment demonstrates that rats are able to lever press during the period between successive self-administered heroin infusions, suggesting that the pausing normally seen between infusions is not due to debilitation, stereotyping, or sedation.

Animals↗
PubMed1985

Brain mechanisms of drug reward and euphoria.

Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate receptors in the periaqueductal gray matter. This receptor population is anatomically distinct from the population mediating the rewarding effects of opiates in nondependent animals. While both opiates and stimulants can activate (though by quite different mechanisms and at quite different loci) the dopaminergic circuitry underlying reward phenomena, only opiates activate the separate circuitry underlying dependence phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Anatomically distinct opiate receptor fields mediate reward and physical dependence.

Rats never before exposed to opioids rapidly learned to press a lever for microinjections of morphine into the ventral tegmental area. Challenge by a narcotic antagonist produced no signs of physical dependence. Dependence was not seen after long-term morphine infusions into the ventral tegmentum but was seen after similar infusions into the periventricular gray region. Thus a major rewarding property of morphine is independent of the drug's ability to produce physical dependence. These data challenge models of drug addiction that propose physical dependence as necessary for the rewarding effects of opioids.

Animals↗
PubMed1984

Brain reward circuitry: four circuit elements "wired" in apparent series.

Activation of a variety of anatomically distinct sites in the central nervous system can produce rewarding states. Four central reward phenomena are amphetamine injections into nucleus accumbens, morphine injections into the ventral tegmental area, electrical stimulation of the ventral tegmental area, and electrical stimulation of the lateral hypothalamic medial forebrain bundle. Current evidence suggests that these four rewarding events trigger activity in elements of a common reward circuit and that the elements are connected in series. The four partially identified elements in this circuit are (1) descending, fast-recovering, short refractory period fibers of the medial forebrain bundle, (2) separate, opioid peptide-containing afferents to the ventral tegmental area, (3) the dopaminergic cells projecting from the ventral tegmental area to nucleus accumbens, and (4) the dopaminoceptive cells of nucleus accumbens.

Animals↗
PubMed1983

Neural substrates of opiate reinforcement.

A major component of opiate reward is derived from a drug action in the ventral tegmental area: (a) rats quickly learn to self-administer morphine directly into the ventral tegmentum, (b) intracranial self-administration into other brain sites is not quickly learned, and (c) narcotic antagonist microinjections into the ventral tegmentum attenuate reward from intravenous heroin infusions. At least one component of opiate reward is dependent on a dopaminergic system: (a) electrophysiological and neurochemical indices suggest that opiates activate ventral tegmental dopaminergic neurons, (b) ventral tegmental opiate infusions are behaviorally activating producing contralateral rotation that is blocked by neuroleptics, (c) reward from heroin is blocked by neuroleptics, and (d) reward from heroin is attenuated by dopamine-depleting lesions of the ventral tegmental system. Brain sites involved in the production of physical dependence on opiates are anatomically distinct from those initiating the acutely rewarding action of opiates. It is theoretically viable that opiates derive their reinforcing impact from a combination of positive and negative reinforcement processes: (a) the neural substrate for the positive reinforcing action probably involves a ventral tegmental dopamine system important in appetitive motivation, and (b) the neural substrate for the negative reinforcing action may involve a periventricular gray system that is independent of the system which mediates the acutely rewarding property of opiates.

Animals↗
PubMed1983

A computer approach to measuring shuttle box activity and conditioned place preference.

A procedure is described for measuring locomotor activity and place preference using an Apple II + computer. The interface consists of a single integrated circuit connected by a 16 pin jumper cable to the Apple's game I/O connector. This approach can be easily adapted to provide sequential reading of one to seven input lines from up to 16 different test boxes. The software is written in basic and doesn't require any knowledge of memory addressing or machine language programming.

Animals↗
PubMed1983

Circling from intracranial morphine applied to the ventral tegmental area in rats.

Crystalline morphine applied unilaterally to the ventral tegmental area in rats caused circling away from the side of application. This circling was reversed by naloxone (3 mg/kg) and blocked by pretreatment with pimozide (0.5 mg/kg). When tested in an open field the animals followed the perimeter of the enclosure; thus the radius of the circles described was determined by environmental rather than central factors. Morphine induced forward locomotion in all four limbs; there were no major signs of postural asymmetry noted in the longitudinal axis of the animal's body. This study suggests that morphine activates a population of A-10 dopamine cells known to be involved in locomotion.

Animals↗
PubMed1982

Action of drugs of abuse on brain reward systems: an update with specific attention to opiates.

In addressing the role that the substrate of brain stimulation reward might play in drug abuse, Wise [47] reviewed evidence relating brain stimulation and psychomotor stimulant reward to dopaminergic but not noradrenergic elements identified with brain reward circuitry. He then speculated that one possible mechanism of opiate, ethanol, barbiturate or benzodiazepine reward might involve a specified disinhibition of the dopaminergic element. He suggested that these drugs might have inhibitory actions on locus coeruleus, which in turn might send an inhibitory projection to the dopaminergic link in reward circuitry. This speculation is challenged with respect to ethanol in the companion article [1] and with respect to opiates in the present article. Recent evidence indicates that the rewarding action of opiates is mediated in the region of the dopaminergic cells of the ventral tegmentum and not in the region of the noradrenergic cells of locus coeruleus. Rewarding opiate injections appear to activate the same or a similar dopaminergic link in brain reward circuitry as that thought to be activated through its afferent inputs in the case of brain stimulation reward and activated at its synaptic terminals in the case of psychomotor stimulant reward. Whether other drugs of abuse activate links in brain reward circuitry which function in parallel or in series with the dopaminergic link identified with opiates and stimulants remains an open question.

Alcohol Drinking↗