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Biomedical subjects

C L Broekkamp

Publications and source records attributed to C L Broekkamp.

At least 73 records · Page 4Linked to original sources
PubMed1983

Strategies for studying the neurochemical substrates of drug reinforcement in rodents.

Results from three different experimental paradigms for studying drug reinforcement are reviewed. Rate-increasing effects of amphetamine on intracranial self-stimulation are abolished by lesions to ascending dopamine neurons. Rate-increasing effects of intracranial microinjection of opioids on self-stimulation are localized to the vicinity of dopamine cell bodies in the ventral tegmentum. Conditioned reinforcement produced with intracranial microinjection of opioids into the ventral tegmental area is blocked by the dopamine antagonist haloperidol and lesions to ascending dopamine pathways. Intravenous self-administration of cocaine is blocked by intracerebral microinjection of spiroperidol into the nucleus accumbens but not into the caudate nucleus. Ascending dopamine neurons appear to mediate some of the reinforcing properties of both psychomotor stimulants and opioids.

Amphetamine↗
PubMed1983

Neurochemical and neuropharmacological indications for the involvement of GABA and glycine receptors in neuropsychiatric disorders.

From binding studies using 3H-GABA and 3H-strychnine in dissected human brain material, inhibitory amino acid neurotransmitter receptors have a widespread distribution in the human CNS. Generally GABA receptors are predominant in the forebrain and upper brainstem whereas glycine receptors are more localized in the lower brainstem and spinal cord. Some areas (eg. the substantia nigra) have appreciable quantities of both receptors. Although glycine receptors are altered in some pathological conditions (eg. in Parkinson's disease, in the substantia nigra) the neuropharmacology of the glycine system is still poorly understood. On the other hand the GABA system has been intensively studied. Dysfunction of GABA receptors occurs in various neurological states, as epilepsy, Parkinson's disease and Huntington's chorea. Furthermore GABA agonists are active in animal models for dyskinesia, epilepsy and depression, amongst others. Clinical studies with progabide confirm these findings in animal models, and suggest that low-medium affinity GABA agonists are more appropriate clinical agents than are high or very high affinity GABA agonists. From these and many other findings there appears to be a very large potential for creating new pharmacological agents for different neuropsychiatric disorders based on agonist activity at inhibitory amino-acid receptors. From the example of progabide these compounds can be made not only specific for the receptor involved, but also to have a lower incidence of neurotoxic effects than presently available drugs.

Central Nervous System↗
PubMed1982

Enhancing GABAergic transmission reverses the aversive state in rats induced by electrical stimulation of the periaqueductal grey region.

In a proposed rat model for anxiety (electrical stimulation of the periaqueductal grey region), progabide (a GABA agonist) and diazepam both increased the latency to escape to a safe compartment and also the current needed to induce the escape response (escape threshold). Furthermore, the effects of progabide and diazepam were greater than additive in their actions on the escape response as when given together in normally subliminal doses, the combination exerted a marked anti-aversive effect. These actions of the drugs alone or in combination could not be explained by non-specific motor effects. Blockade of GABA receptors by bicuculline greatly reduced or abolished the action of progabide and diazepam (single administration). Sodium valproate, which indirectly augments GABAergic transmission, also increased the escape latency and escape threshold whereas, in contrast, diphenylhydantoin accentuated the aversive effects of stimulation of the periaqueductal grey. Haloperidol increased the escape latency and threshold but not other signs of distress following central stimulation (vocalization, jumping) which were effectively blocked by progabide and diazepam. The action of haloperidol was completely explicable by an interference with motor mechanisms. These results are interpreted as an indication that GABA agonists have an anti-aversive action in this proposed rat model for anxiety and, furthermore, that GABA receptors at least partially mediate the actions of benzodiazepines in this model.

Animals↗
PubMed1981

Involvement of the amygdala in the effect of antidepressants on the passive avoidance deficit in bulbectomised rats.

In the present study the role of the amygdala is demonstrated in the effect of antidepressant drugs on passive avoidance learning in bulbectomised rats. Imipramine, amitriptyline, or fluoxetine injected bilaterally (2 X 10 microgram) into the medial part of the amygdala improves passive avoidance learning by bulbectomised rats. Systemic pretreatment with metergoline attenuates the effect of local imipramine or fluoxetine injection. Microinjection of serotonin but not noradrenaline into the amygdala improves passive avoidance learning by bulbectomised rats. The relevance of the amygdala in the behavioral effects of antidepressants in animals is discussed.

Amitriptyline↗
PubMed1981

Involvement of caudate nucleus, amygdala or reticular formation in neuroleptic and narcotic catalepsy.

Local injection of haloperidol into the caudate nucleus produced catalepsy in contrast to the weak effects of morphine injected at the same site. Injection of either haloperidol or morphine into the amygdala did not have any cataleptogenic effect. Both haloperidol and morphine produced catalepsy when injected into the reticular formation. Naloxone injected into the reticular formation completely reversed the catalepsy following intraperitoneal morphine but not haloperidol. Pretreatment with alpha-methyl-p-tyrosine potentiated the effect of haloperidol injected into either the reticular formation or caudate nucleus. Phentolamine but not lignocaine or metergoline, injected into the reticular formation also caused a cataleptic response. The results confirm the caudate nucleus as a site for haloperidol catalepsy and in addition, suggest the reticular formation as a primary site for morphine catalepsy and a secondary site for haloperidol catalepsy; additionally a noradrenergic modulation of catalepsy may occur within this brainstem region.

Amygdala↗
PubMed1980

Serotonin-mimetic and antidepressant drugs on passive avoidance learning by olfactory bulbectomised rats.

Olfactory bulbectomised rats were treated with drugs and their rate of acquisition of a passive avoidance task was measured. The acquisition-rate, which is disturbed by the bilateral ablations, was completely restored by acute administration of fenfluramine or fluoxetine. Partial restoration was found with quipazine. Clonidine was without effect. Repeated treatments with imipramine and mianserine improved passive avoidance of bulbectomised rats. Metergoline blocked these effects of imipramine and mianserin. These results indicate a serotonergic mechanism in the effect of antidepressants on olfactory bulbectomised rats.

Animals↗
PubMed1979

Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area.

The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites. Bilateral injections of morphine (2 x 1 microgram) into the ventral tegmental area and substantia nigra produced the strongest enhancement at the shortest latencies. At these sites, bilateral injections of 200 ng of morphine also produced a significant enhancement whereas a dose of 50 ng was below threshold for the rate increasing effect. The enhancement by morphine was effectively antagonized by naloxone (5 mg/kg). When injected bilaterally into the same area, D-Ala2-Met5-enkephalinamide (2 x 1 microgram) also induced a strong enhancement of self-stimulation lasting for 70 minutes. A possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.

Animals↗
PubMed1978

Atonia after carbachol microinjections near the locus coeruleus in cats.

The effect of microinjections of carbachol into the dorsolateral pontine tegmentum on the behaviour of cats is investigated. Injections of small amounts (50 and 500ng) of carbachol into the pontine reticular formation induced muscular atonia in otherwise awake animals. The atonia is not due to cholinergic stimulation of the noradrenergic cells of the locus coeruleus or the dorsolateral pons, since the most effective sites were situated ventrally to the locus coeruleus and alpha- and beta-adrenergic blocking agents did not affect the antonia. The results are discussed in view of the postulated role of the locus coeruleus in paradoxical sleep.

Animals↗
PubMed1977

Subcutaneous injections of apomorphine, stimulus generalization and conditioning: serious pitfalls for the examiner using apomorphine as a tool.

This report shows that stimulus generalization occurs in rats conditioned by a single injection of apomorphine. The data suggest that apomorphine initially acts as an unconditioned stimulus (UCS) of an unconditioned response (UCR) that, in turn, produces stimuli which become conditioned stimuli (CS) of a conditioned response (CR) having a nature identical to that of the UCR. The study also shows that behaviour elicited by a subcutaneous injection of apomorphine depends on the part of the body selected for administration. The mentioned properties should be taken into account when apomorphine is used as a tool in studies on brain and behaviour.

Animals↗
PubMed1976

Separation of inhibiting and stimulating effects of morphine on self-stimulation behaviour by intracerebral microinjections.

The effects on self-stimulation behaviour of 5 mug morphine HCl applied into the ventricular system and into different areas throughout the brain were studied. Injections into the ventricular system and in areas intermediate between the posterior hypothalamus and the periaqueductal grey matter had biphasic effects: an inhibition followed by an excitation. Injections into the posterior hypothalamus resulted in increased self-stimulation whereas injections into the periaqueductal grey matter and into the locus coeruleus were only inhibiting.

Animals↗
PubMed1975

The effect of microinjections of amphetamine into the neostriatum and the nucleus accumbens on self-stimulation behaviour.

The effect of micro-injections of dexamphetamine chloride into the neostriatum, the nucleus accumbens, the anterior hypothalamus, and the ventricular system on self-stimulation with electrodes in the ventral tegmentum was studied. Unilateral injections of 10 mug into the anterior hypothalamus produced no effect. Injections into the neostriatum tended to depress the self-stimulation rate, whereas injections into the nucleus accumbens increased the rate markedly. Bilateral injections (2 times 2.5 mug and 2 times 5 mug amph.) into the nucleus accumbens were more effective than unilateral injections and were as effective as systemic injections of 1 mg/kg amphetamine (i.p.). Bilateral injections into the neostriatum also increased the self-stimulation rate. Injections of 10 mug into the ventricular system resulted in a smaller increase which was not statistically significant. These results are discussed in relation to the involvement of the dopaminergic system in the maintenance of self-stimulation behaviour.

Animals↗