Inhibition of amphetamine-induced locomotor activity by injection of carbachol into the anterior hypothalamic/preoptic area: Pharmacological and electrophysiological studies in the rat (original) (raw)
Brain Research, 1986
Cholinergic elements in forebrain structures are implicated in locomotion but their role is still unclear. In the present study, the effects of intracerebrally injected carbachol or atropine on spontaneous locomotion and rearing activity were investigated. Effective injection sites were found in the area between frontal planes 5.3 and 6.3 mm from interaural plane and between the ventricle wall and lateral plane 1.1 mm from the midline which corresponds to the medial anterior hypothalamic/preoptic area. Injections of 1.0 #g of carbachol into this area decreased locomotor activity and rearing to one-third of the control level during the firs[ 5 min of recording. These reductions of locomotion and rearing were dose-dependent and reversed by 1.5/~g of atropine. Atropine alone, at this dose, had no effect on locomotion but higher doses (20.0-60.0/~g) of atropine produced a dose-dependent increase of locomotion. A comparison of the injection sites with recent maps of the cholinergic system indicates that muscarinic cholinoceptive, presumably non-cholinergic, cells throughout the medial AH/POA might be associated with a decrease of locomotor activity caused by intracerebral injections of carbachol.
Brain Research, 1985
Injections of amphetamine into the nucleus accumbens increased locomotor activity of rats. St,bsequent in ections of procaine into the midbrain, in the region of the pedunculopontinc nucleus, significantly reduced the amphetamine-induced locomotor activit~. Control experiments showed that procaine injections into the contralateral pedunculopontine nucleus had little or no effect, as well as ipsilateral injections dorsal and ventral to the pedunculopontine nucleus. These findings suggest that release of dopaminc trom amphetamine injections into the accumbens gives rise to ipsilateral descending influences on the region of the pedunculopontine nucleus, a major component of the mesenccphalic locomotor region. Descending influences from the nucleus accumbens to mcsencephalic locomotor region may serve as a link for limbic-motor integration in behavioral response initiation.
Pharmacology Biochemistry and Behavior, 1976
~Lffects on self-sthnulation b~ caudate or hypothalamus of the squirrel monkey. PIIARMAC. BIOCHEM. BEHAV. 5(2) [149][150][151][152][153][154][155][156] 1976. -In 2 separate groups of squirrel monkeys and within 3 animals low rates of intracranial self-stimulation (ICSS) elicited from caudate or lateral hypothalamic brain sites were increased by as much as 200% above control levels by amphetamine (0.5 mg/kg). Thresholds for responding were decreased by 50%. Increasing the drug dose from 2 to 10 mg/kg produced response inhibition at both brain sites. The duration of inhibitory action of amphetamine (2.0 mg/kg) on ICSS from the medial forebrain bundle (MFB) area of the lateral hypothalamus was 6 hr. At caudate sites ICSS did not occur until 48 hr had elapsed. A 10 mg/kg dose of amphetamine produced a duration of action of 36 hr in the MFB and 84 hr in the caudate. Chlorpromazine (CPZ) doses of 0.5 and 1.0 mg/kg decreased caudate ICSS significantly more than lateral hypothalamic ICSS. At 1.0 mg/kg the duration of action of CPZ was 6 hr at lateral hypothalamic brain sites and 24 hr at caudate sites. At a 2.0 m,g/kg CPZ dose the duration of action was 12 hr in the MFB and 36 hr in the caudate. A dose of 0.10 mg/kg of clonidine blocked high rates of MFB ICSS while within the same animal caudate ICSS was much less affected. Higher doses (0.25 mg/kg) sedated the animal and ICSS was equally inhibited at both sites. These findings, using ICSS as a behavioral measure, suggest that the effects of amphetamine and CPZ involve not only hypothalamic structures but more anterior telenccphalic sites as well. The prolonged actions of amphetamine and CPZ on caudate ICSS suggest that drugs acting, in part. on dopamine containing neurons will interfere with certain caudate mediated behavior. Further, since hypothalamic but not caudate ICSS sites are more dose sensitive to drugs that selcctivcly act on NE containing neurons, other amines in addition to NE may play a role in the support of 1CSS.
Neuropharmacology, 2000
Recently, it was reported that blocking metabotropic glutamate receptors (mGluRs) in the rat nucleus accumbens (NAcc) prevents the generation of locomotion by amphetamine (AMPH) in this site. In these studies, the non-selective group I/group II mGluR antagonist (R,S)-α-methyl-4-carboxyphenylglycine [(R,S)-MCPG] was used. The present study used more selective receptor antagonists to examine the specific contribution of group I and group II mGluRs to this effect. When co-injected bilaterally with AMPH into the NAcc, the group II selective mGluR antagonist (2S)-α-ethylglutamic acid [EGLU; 0.5-5.0 nmole/side] dose-dependently blocked the locomotion and rearing produced by AMPH. Equimolar concentrations of the group I selective antagonist (R,S)-1aminoindan-1,5-dicarboxylic acid [AIDA; 0.5-5.0 nmole/side] were without effect. As previously reported for (R,S)-MCPG, neither of these receptor antagonists produced locomotor effects when injected alone in these concentrations into the NAcc. These results suggest that group II, but not group I, mGluRs in the rat NAcc contribute importantly to the ability of AMPH to produce locomotor activation.
Psychopharmacology, 1988
Lesion studies employing 6-hydroxydopamine (6-OHDA) suggest that locomotor hyperactivity induced by certain stimulant drugs is dependent on dopaminergic neurotransmission in the nucleus accumbens (NACC). However, studies to date have not adequately controlled for the reported effects of 6-OHDA on baseline (non-drug) activity and on DA levels in other terminal regions. Slow bilateral infusions of 6-OHDA into the NACC, but not into olfactory tubercle (OT) or medial prefrontal cortex (mPFCx), reduced d-amphetamine (0.5 mg/kg SC) hyperactivity and resulted in a "supersensitive" (hyperactive) response to a low dose of apomorphine (0.1 mg/kg SC) in photocell cages. Direct observation revealed no behavioral changes in OT lesioned rats challenged with apomorphine which might correspond to a "denervation supersensitivity" syndrome. Assays of DA and 5-hydroxytryptamine (5-HT) in mPFCx, OT, NACC, and caudate-putamen revealed that 6-OHDA infusion into NACC caused substantial DA loss in NACC, OT and mPFCx, whereas infusion at mPFCx or OT sites depleted DA locally (>85% loss) with little or no remote change. Concentrations of 5-HT were little altered by 6-OHDA, except for a local depletion in mPFCx. The present results confirm the importance of nucleus accumbens DA in the expression of locomotor stimulation induced by apomorphine and d-amphetamine, and suggest that the mPFCx and OT do not make an important contribution.
Neuropeptides, 2003
The role played by the biologically active CART 55-102 peptide in NAcc AMPH induced locomotion was investigated. When microinjected alone into this site, none of the doses of CART 55-102 tested (0.1, 0.4, 1.0 or 2.5 lg/0.5 ll/side) produced effects on locomotion during a two-h test. However, when co-injected with AMPH (2.5 lg/0.5 ll/side) into the NAcc, moderately high (2.5 lg/ side) and middle to high (0.4-2.5 lg/side) doses of CART 55-102 significantly attenuated the effects of AMPH on locomotion and rearing, respectively. These results indicate that CART peptides can exert an antagonistic effect on the generation of locomotion by AMPH in the NAcc.
Increased amphetamine-induced locomotion during inactivation of the basolateral amygdala
Behavioural Brain Research, 2004
At low doses, amphetamine has been shown to produce reliable increases in locomotor activity through its actions on the mesolimbic dopamine (DA) terminals in the nucleus accumbens (NAC). The basolateral amygdala (BLA) has recently been reported to have anatomical projections to the NAC, suggesting that it might serve to alter or modulate the function of the NAC. To test this hypothesis, the current experiment produced lidocaine-reversible lesions of the BLA and assessed changes in NAC function by examining alterations in locomotor activity in response to s.c. amphetamine (2mg/kg). While BLA inactivation alone was found to have no effect on spontaneous or basal locomotor activity, it produced a significant potentiation of amphetamine-induced hyperactivity. These results suggest that BLA inactivation removes a system that inhibits the locomotor response to amphetamine. The data are, therefore, consistent with the view that the BLA may serve to modulate NAC function.