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C J Pycock

Publications and source records attributed to C J Pycock.

34 records · Page 2Linked to original sources
PubMed1977

Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei.

Changes in stereotyped sniffing, biting and hyperactivity induced by apomorphine and D-amphetamine in the rat were determined after bilateral 6-hydroxy-dopamine (6-OHDA) lesions (8-16 micron/4micron6) of the extrapyramidal caudate-putamen (CP) (anterior and centre), globus pallidus (GP) and substantia nigra (SN), the mesolimbic nucleus (ACB), tuberculum olfactorium (TUO) and central amygdaloid nucleus (ACE). Lesions were also induced in the medial forebrain bundle in the lateral hypothalamus (LH). The 6-OHDA lesions of the CP reduced amphetamine biting but not sniffing or hyperactivity. Centrally placed 6-OHDA failed to modify any response to apomorphine but anterior locations reduced apomorphine biting. Both lesion locations led to a 45-65% reduction in striatal dopamine (DA) content, but the anterior location also involved depletions of mesolimbic DA. 6-OHDA lesions of the GP reduced striatal DA by 62% but initially potentiated before reducing both apomorphine and amphetamine biting. These lesions also potentiated amphetamine hyperactivity but other parameters were unmodified. The LH and SN lesions reduced striatal and mesolimbic DA by 75-80% and potentiated apomorphine biting. The LH lesions reduced amphetamine biting and hyperactivity but the SN lesions initially potentiated these responses. 6-OHDA lesions of the ACB reduced the DA content of this nucleus by 72% but had little effect on the TUO: these lesions reduced the duration of amphetamine hyperactivity and potentiated apomorphine biting. In contrast, equally selective lesions of the TUO (80% DA depletion) enhanced the locomotor activity response to both apomorphine and amphetamine; apomorphine biting was also increased but other parameters were unmodified. Lesions of the ACE depleted amygdaloid DA by at least 80% and reduced or abolished apomorphine and amphetamine biting in the chronic stage. The results indicate that the sites for mediation of sterotyped sniffing, biting or hyperactivity are not the same for apomorphine and amphetamine, and that each behavioural state involves the functioning of more than one DA-containing area.

Amygdala↗
PubMed1977

The interaction of clonidine with dopamine-dependent behaviour in rodents.

The effect of clonidine on a number of behavioural parameters believed to be expressed through central dopaminergic mechanisms has been studied in rodents. 1. Clonidine (0.06-2 mg/kg) potentiated the circling response to standard doses of both apomorphine (0.25 mg/kg) and amphetamine (3 mg/kg) in mice with unilateral destruction of nigro-neostriatal dopamine nerve terminals. Similarly, clonidine (0.06-2 mg/kg) enhanced the locomotor effect of apomorphine in reserpinised mice. 2. Clonidine (0.5 mg/kg) was without effect on the patterns of stereotypyd behaviours induced by the dopamine agonist apomorphine (0.1-5 mg/kg) in the rat. Unilateral intrastriatal injections of clonidine (5-100 microng) caused no discernable behavioural effects in rats. 3. Injection of apomorphine (10 microng) bilaterally into the region of the nucleus accumbens of the rat resulted in a hyperactive response, while bilateral injection of clonidine (50 microng) into this region caused marked sedation, thus mimicking the effects of these drugs on motor activity when administered systemically. Combinations of systemic or nucleus accumbens apomorphine and clonidine resulted in potentiated stereotype and prolonged hyperactivity responses. 4. Clonidine (0.5 mg/kg) potentiated the cataleptic effect of the dopamine antagonist haloperidol (0.1-2 mg/kg) in rats. Clonidine therefore potentiated those behavioural responses exhibiting a locomotor component (viz. circling and hyperactivity), but was without effect on stereotypy. The potentiation of catalepsy induced by clonidine may be explained in non-specific sedatory terms. It is apparent that clonidine acts through a secondary neurone system which modifies the effects of dopamine receptor stimulation, although the exact site of this interaction is not clear. The tentative conclusion might be that clonidine inhibits 5-HT neuronal activity, and the possible relationships between 5-HT and NA and dopamine are discussed.

Animals↗
PubMed1977

Circling behavior in rodents following an imbalance of basal ganglia GABA concentrations.

Unilateral focal injection of the GABA - transaminase inhibitor, ethanolamine O-sulphate, into one substantia nigra or globus pallidus of rats or the striatum of mice induces spontaneous and drug-induced circling behaviour. Circling parallels the imbalance of GABA concentrations between the injected and the noninjected side of the brain, being most striking on Day 1 and 3, and non-existent by Day 7. Increases in GABA concentration were demonstrated in areas distant from the injection site, on both the injected and noninjected side of the brain presumably due to diffusion of the ethanolamine O-sulphate. This diffusional effect made it impossible to define the exact site of GABA and dopamine interaction.

4-Aminobutyrate Transaminase↗
PubMed1976

The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain.

The importance of extrapyramidal and mesolimbic function for circling behaviour was investigated by placing 6-hydroxydopamine (6-OHDA) and electrolesions in the cell bodies, axons and terminals of each system. Circling behaviour was weak when 6-OHDA was placed at the centre of the substantia nigra (SN), but the characteristic contralateral/ipsilateral turning to apomorphine/amphetamine were recorded. Circling was more marked when 6-OHDA was placed anterior to the SN but was generally absent following injections posterior to the SN. However, 6-OHDA placed in the medial forebrain bundle in the lateral hypothalamus resulted in intense contralateral/ipsilateral turning to apomorphine/amphetamine. Generally, the intensity of circling responses was related to the degree of striatal dopamine (DA) depletion but the more effective lesions also caused reductions in mesolimbic DA content. However, circling was not observed following any 6-OHDA injection into the mesolimbic DA system and it is concluded that mesolimbic DA function is not essential for the initiation of circling. In contrast to the 6-OHDA lesions, rats circled ipsilateral to both apomorphine and amphetamine when the SN was damaged by electrocoagulation to cause marked depletion of striatal dopamine. Lesser depletions of striatal dopamine after electrocoagulation in different regions of the medial forebrain bundle were associated with a lower intensity of ipsilateral circling to both drugs. In general, the differences between 6-OHDA and electrolesions could not be explained by additional damage to ascending noradrenaline or 5-hydroxytryptamine pathways. Lower doses of apomorphine were effective in the 6-OHDA circling rats, and the ipsilateral striatum of such rats was more sensitive to directly applied DA. Higher doses of apomorphine were required to produce circling after chronic electrolesions which rendered the ipsilateral striatum insensitive to DA. The contralateral circling to apomorphine after 6-OHDA lesions was abolished by chronic but not by acute electrolesion of the SN. It is suggested that electrolesions of the SN cause different effects to 6-OHDA because they destroy neuronal pathways in addition to the dopaminergic nigrostriatal tract. These appear to be required for the expression of circling behaviour caused by stimulation of the denervated striatum. Whereas 6-OHDA lesions result in super-sensitivity of the denervated strital DA receptors, electrolesions may cause a hypo-sensitivity of the same receptor sites.

Afferent Pathways↗
PubMed1976

Possible GABA-mediated control of dopamine-dependent behavioural effects from the nucleus accumbens of the rat.

The effect of elevating GABA levels in the region of the nucleus accumbens on various dopamine-dependent behaviours in the rat has been studied. The GABA-transaminase inhibitor, ethanolamine O-sulphate (EOS) was injected bilaterally (through a needle angled at 45 degrees) into the nucleus accumbens. This resulted in a 4-5 fold increase in the GABA concentrations in the mesolimbic areas on day 1, a 2-fold increase on day 3, and a return to normal by day 7. Moderate increases in striatal and cortical GABA levels were also seen on days 1 and 3. At all times animals exhibited normal spontaneous activity and exploratory behaviour in a hold-board apparatus. However, on day 1, when mesolimbic GABA levels were maximal, a low dose of systematically administered amphetamine (0.5 mg/kg) did not induce the increased locomotor activity seen in a control group of animals. Similarly on day 1, the direct injection of dopamine into the nucleus accumbens of rats previously injected with EOS did not evoke the usual hyperactivity response. This response returned to normal on day 7. Apomorphine-induced stereotyped behaviour patterns observed on days 1 and 2 did not significantly differ in those rats previously injected with EOS with animals of a control group. A possible GABA-mediated control of dopaminergic mechanisms in the nucleus accumbens is suggested, and the possible site of interaction discussed.

4-Aminobutyrate Transaminase↗
PubMed1976

Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice.

1. The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2. Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3. Parachlorophenylalanine (3 X 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4. Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5. Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6. The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7. The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.

Amphetamines↗
PubMed1975

Circling behaviour produced by unilateral lesions in the region of the locus coeruleus in rats.

Rats with unilateral lesions in the region of the locus coeruleus circled tightly to the opposite side when given apomorphine or amphetamine. This turning behaviour was transient and disappeared within some 30 days after surgery. It was seen most obviously in animals with severe unilateral destruction of the locus coeruleus, which caused on average a 55% reduction in the level of noradrenaline in the ipsilateral cerebral cortex. It was not marked in animals with partial unilateral lesions of the locus coeruleus, which caused only an average fall in cortical noradrenaline of 22%. It was not seen in sham operated animals or animals in which lesions were placed into adjacent structures such as the cerebellum above, superior cerebellar peduncle laterally, and brain stem ventrally. A clue to the mechanism of this phenomenon may lie in the observation that dopamine in the ipsilateral striatum was increased 5 days after operation, when circling occurred, but had returned to normal by 30 days when circling had ceased. It is suggested that the lesion causes a reduction in impulse traffic in the ipsilateral nigrostriatal pathway, and that circling is due to preferential stimulation of the ipsilateral striatal dopamine receptors by both drugs; apomorphine directly, amphetamine by release of endogenous dopamine.

Amphetamine↗
PubMedDate not supplied

Central deopaminergic receptor supersensitivity and its relevance to Parkinson's disease.

The degeneration of the substantia nigra that characterises Parkinson's disease may cause an alteration in sensitivity of striatal dopamine receptors. The development of denervation supersensitivity has been held to be responsible for some of the effects of chronic levodopa therapy. The rotating rodent is an animal model commonly used to study the phenomenon of striatal dopamine receptor supersensitivity, and to investigate drugs which may prove to be beneficial in the treatment of Parkinson's disease. We have investigated as to whether long-term oral administration of levodopa to mice with unilateral destruction of striatal dopaminergic nerve terminals influences dopaminergic receptor denervation supersensitivity as judged by the circling response following systemically administered levodopa. It does not do so and the relevance of these findings to the treatment of Parkinson's disease is discussed.

Animals↗