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Biomedical subjects

W A Corrigall

Publications and source records attributed to W A Corrigall.

At least 55 records · Page 3Linked to original sources
PubMed1989

Heroin self-administration by rats: influence of dose and physical dependence.

Lever-pressing behavior reinforced by intravenous infusion of various concentrations of heroin, and consequent development of physical dependence, were examined in rats. In addition, the influence of opiate dependence, and of its disappearance following withdrawal, on heroin self-administration were investigated. It was found that intravenous self-administration of heroin at 0.03 mg/kg/infusion maintained self-administration behavior without producing physical dependence. Total responses per session decreased with increasing unit dose of heroin, whereas the total amount of drug self-administered was directly related to unit dose. Significantly greater numbers of withdrawal signs and percentage body weight losses in response to naloxone injections were observed following self-administration of heroin at 0.1, 0.3 or 0.6 mg/kg/infusion. Intake of heroin at 0.03 mg/kg/infusion, but not at 0.1, 0.3 or 0.6 mg/kg/infusion, was found to increase significantly in opiate-dependent and postdependent animals. These findings support the previous use of 0.03 mg/kg/infusion as a suitable dose for illustrating the reinforcing effect of heroin without the influence of physical dependence.

Animals↗
PubMed1989

Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment.

Rats that had been trained to respond for food on a fixed-interval 3-minute schedule were treated once daily with nicotine (2 mg/kg) for 50 days. Animals developed marked tolerance to the depressant effect of nicotine as measured by the decreased effect of the treatment dose on response rates over days. Substitution of saline for nicotine during chronic treatment resulted in response rates which were significantly less than pretreatment values. In addition, following cessation of chronic treatment, response rates were initially suppressed below pretreatment rates; by the third day of withdrawal, response rates had returned to baseline levels. It is proposed that the response deficit observed during nicotine absence represents one behavioral component of a nicotine withdrawal syndrome.

Animals↗
PubMed1988

Evidence for opioid mechanisms in the behavioral effects of nicotine.

The effects of nicotine, heroin, mecamylamine, and naltrexone were studied in rats trained to respond under a fixed-interval 3-min schedule of food presentation. Nicotine (0.1-3.0 mg/kg) first increased, then decreased response rates; heroin (0.03-0.6 mg/kg) produced only dose-related response rate decreases. Mecamylamine (0.1-3.0 mg/kg) and naltrexone (0.3-10.0 mg/kg), administered alone, each had little effect on response rates. However, when administered in combination with increasing doses of nicotine, mecamylamine (1.0 mg/kg) blocked the increases in response rate caused by 0.3 and 1.0 mg/kg nicotine and partially reversed the decreases in rate caused by 3.0 mg/kg nicotine. In contrast, the combination of naltrexone and nicotine, at doses of each that alone either had no effect or increased response rates, markedly decreased responding. This phenomenon was not evident during the first pairing of naltrexone and nicotine, but appeared in the second and subsequent pairings. After drug combinations had been tested, the nicotine dose-response curve was unchanged from its previous values, and naltrexone alone produced no tendency to decrease response rate. These observations may be related to previous results that have suggested a role for endogenous opioids in mediating certain of the behavioral effects of nicotine.

Animals↗
PubMed1988

Conditioned place preference produced by intra-hippocampal morphine.

Unilateral microinjections of morphine sulphate into the rat hippocampus were found to produce a conditioned place preference, whereas equi-volume saline injections into the same region in a separate control group were without effect. The results are discussed in terms of possible reward or habituation functions of the hippocampus.

Animals↗
PubMed1988

Antagonist treatment in nucleus accumbens or periaqueductal grey affects heroin self-administration.

The role of opiate receptors in the periaqueductal grey and nucleus accumbens in maintenance of intravenous heroin self-administration was examined by means of intracranial microinjections of the quaternary opiate antagonist methyl naltrexone. Over a dose range of 0-3.0 micrograms, pre-session infusions of methyl naltrexone in either brain site produced dose-related increases in responding for heroin (0.06 mg/kg/infusion) on a CRF schedule, without causing significant changes in responding on a second activity control lever. Involvement of the periaqueductal grey was also examined in animals administering a lower heroin dose (0.03 mg/kg/infusion) in shorter sessions in order to minimize drug exposure prior to treatment. In this experiment, infusion of methyl naltrexone produced selective increases in responding for heroin, whereas treatment with the identical dose of methyl naltrexone had no effect on cocaine self-administration (1.0 mg/kg/infusion) in the same animals. With respect to the nucleus accumbens, these data confirm its involvement in opiate self-administration. Data for the periaqueductal grey provide the first evidence that opiate receptors in the vicinity of this brain region may play a role in intravenous opiate self-administration.

Animals↗
PubMed1987

Heroin self-administration: effects of antagonist treatment in lateral hypothalamus.

The involvement of the lateral hypothalamus and medial prefrontal cortex in mediating heroin self-administration was examined by means of intracranial microinjections of the quaternary opiate antagonist methyl naltrexone over a dose range of 0-3.0 micrograms. In animals trained to respond on a continuous reinforcement schedule for intravenous heroin (0.03 mg/kg/infusion), microinfusions of antagonist into the lateral hypothalamus prior to a self-administration session produced significant dose-related increases in responding on the drug manipulandum, similar to increases in responding observed after treatment with naltrexone systemically. Microinfusions of quaternary antagonist into the medial prefrontal cortex over the same dose range effective in the lateral hypothalamus did not produce response increases. These data suggest that opiate action in the lateral hypothalamus, but not in the medial prefrontal cortex, is salient in maintenance of intravenous self-administration.

Animals↗
PubMed1987

Effects of opiate antagonist treatment into either the periaqueductal grey or nucleus accumbens on heroin-induced locomotor activation.

The role of opiate receptors in the periaqueductal grey (PAG) and nucleus accumbens (NA) in the expression of heroin-induced locomotor activation was investigated. Rats received subcutaneous injections of heroin (0.5 mg/kg) in combination with intra-PAG or intra-NA microinjections of the quaternary opiate antagonist methyl naltrexone (MN) in doses of 0.0 (saline vehicle), 0.3, 1.0 and 3.0 micrograms. When injected into the NA, all three doses of MN were found to attenuate heroin-induced locomotor activity compared to saline vehicle. In contrast, intra-PAG MN treatment did not have any significant effect on heroin-induced locomotor activity. With regard to the NA, these results confirm previous findings showing that blockade of NA opiate receptors attenuates heroin-induced locomotor activity. The lack of effect in the PAG indicates that PAG opiate receptors do not participate in the expression of heroin-induced locomotor activation. The implications of these results for the anatomical overlap found between sites mediating opiate reward and locomotor activation are discussed.

Animals↗
PubMed1987

Effects of naloxone on hippocampal seizure activity.

Although the presence of several types of opiate receptors and ligands has been demonstrated within the hippocampus, little is known about the circumstances in which endogenous opiates may be released. Previous studies have suggested that opiates may be involved in producing seizure activity within the hippocampus, or alternatively, that they may be released by seizure activity within the limbic system to prolong the period of postictal depression and thereby prevent the recurrence of seizures during this period. In this experiment we examined the effect of opiate receptor blockade produced by 20 mg/kg ip naloxone on the duration of afterdischarge produced by high-frequency hippocampal stimulation and on inhibition of subsequent seizure activity in male Sprague-Dawley rats. Contrary to the stated hypotheses, naloxone had no effect on either measure.

Animals↗
PubMed1986

An analysis of the paradoxical effect of morphine on runway speed and food consumption.

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference.

Animals↗
PubMed1984

Effects of morphine and naloxone on hippocampal CA3 field potentials following systemic administration in the freely-moving rat.

The effect of IV morphine, 2, 6 and 15 mg/kg, on hilar-evoked CA3 field potentials was studied to determine if this area would be more sensitive to mu-type opiate agonists than the CA1 or dentate regions. In addition, the effect of IV naloxone, 2 and 25 mg/kg, on the same responses was studied to determine if endogenous opiates reported to be present in the mossy fibers are released by electrical stimulation of this pathway. Neither morphine nor naloxone had an effect on CA3 field potentials at any dose used. The CA1 region of the hippocampus is the area most sensitive to morphine, and this effect of morphine correlates best, anatomically, with the localization of mu-receptors identified by the binding of dihydromorphine. Physiological release of endogenous opiates from the hippocampus remains to be shown.

Animals↗
PubMed1983

Opiates and the hippocampus: a review of the functional and morphological evidence.

In spite of a small number of opiate receptors, recent electrophysiological studies have shown that exogenously applied opiates have a powerful excitatory effect on the principal neurons of the hippocampus. These studies have spawned a reconsideration of opiate binding sites in the hippocampus and investigations of the presence of endogenous opiates within this limbic area. This literature, as well as the relevant behavioral studies, is reviewed, and questions of the role of hippocampal opiates and their binding sites are raised.

Animals↗
PubMed1982

Effects of morphine on CA1 versus dentate hippocampal field potentials following systemic administration in freely-moving rats.

Hippocampal field potentials were recorded in vitro before and after a series of incremental doses of morphine (2, 6 and 15 mg/kg i.v.) and after a subsequent infusion of 2 mg/kg naloxone. The 15 mg/kg dose of morphine resulted in an augmentation of the field potential recorded in CA1 following stimulation of stratum radiatum, as shown by an increase in the size of the primary spike and the appearance of (an) additional population spike(s). This was the same effect that was previously observed on the same response in the isolated hippocampal slice following bath application of the drug, suggesting that the hippocampal slice is a valid model for the effects of systemically-administered opiates in this area of the brain. In contrast, morphine generally resulted in an increase in the primary spike only (and no secondary spikes) in the field potentials recorded in dentate following stimulation of the ipsilateral perforant path. In addition, 6 and 15 mg/kg of morphine reduced the attenuation of the second response of a paired-pulse paradigm in the radiatum-to-CA1 reponses, but not in perforant path-to-dentate responses. In 4 out of the 16 animals tested in this experiment, the excitatory effects on the field potentials were accompanied by seizure-like activity in the simultaneously-recorded cortical and hippocampal EEGs, providing further evidence that opiates may mediate convulsive activity in the hippocampus.

Animals↗
PubMed1982

Plasma protein binding of phencyclidine.

In healthy male subjects (n = 12) phencyclidine (PCP) free fraction was 22.0 +/- 2.8 % (mean +/- SD). In male patients with mild to moderate alcoholic liver disease (n = 16) free fraction (23.0 +/- 3.4%) was of the same order as in healthy subjects although age and the concentrations of albumin, bilirubin, and high-density lipoproteins were different (P less than 0.05). Free fraction (76.2 /+- 0.06%) in fatty acid free human serum albumin (HSA, 4.4 gm/dl) was far greater than in plasma. Both the increased binding of PCP in plasma over HSA and the lack of a difference in PCP binding between normals and patients was associated with alpha 1-acid glycoprotein (alpha 1-AGP). This protein is an acute-phase reactant that binds cationic drugs and rises nonspecifically in a variety of diseases. Free fraction of PCP in alpha 1-AGP (75 mg/dl) was 36.4 +/- 1.7%. Half of the variance in PCP binding can be accounted for (r = 0.67, P less than 0.01) from percentage of free PCP = 39.24 - 2.18 (albumin) - 0.094 (alpha 1-AGP). Male rats (n = 14, weight = 251 +/- 7 gm) were alternatively assigned to pretreatment with either saline or alpha 1-AGP (11.6 mg) by cardiac puncture. PCP brain concentrations were reduced (11%, P less than 0.05) in the protein-treated group 5 min after cardiac 3H-PCP (0.17 mg) administration, demonstrating that increased plasma protein binding can reduce free drug concentration during the distribution phase and, thereby, the rate and extent of drug distribution.

Adult↗
PubMed1981

Are endogenous opiates involved in potentiation of field potentials in the hippocampus of the rat?

Changes in hippocampal CA1 field potentials during and after tetanic stimulation were studied in rats pretreated with 5 mg/kg s.c. naloxone or saline. Stimuli consisted of successive tetani of increasing frequency; responses at threshold, midrange and asymptotic intensities were sampled. A several fold increase in response amplitude occurred during low frequency stimulation, with no significant differences between the groups. Post-tetanic responses showed depression at the lower frequencies but increases ranging up to 400% at higher frequencies, with the greatest potentiation at threshold; again there were no significant differences between naloxone and saline groups, suggesting that endogenous opiates are not involved.

Animals↗
PubMed1981

Effect of low concentrations of ethanol on CA1 hippocampal neurons in vitro.

The effects of ethanol (10, 20, 50, and 100 mM) have been studied on field potentials in the CA1 region of the in vitro hippocampal slice preparation. Ethanol produced depression of the orthodromically evoked CA1 population spike and raised the threshold for orthodromic spike production. The effects of ethanol on the size of the population spike were highly correlated with the amount of the inhibition present in the slice as measure by paired pulse stimulation in control medium. Ethanol increased recurrent inhibition in the slice but had no significant effect on the antidromic response and produced only small changes in the dendritic field potential amplitudes. Adaptation or acute tolerance to the depressing effects of ethanol was observed in many slices. It is suggested that ethanol acts by potentiating the intrinsic inhibitory system in the hippocampus.

Action Potentials↗