Effects of lesions of the ventral medial tegmentum on locomotor activity, biogenic amines and response to amphetamine in rats (original) (raw)
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Pharmacology Biochemistry and Behavior, 1994
The locomotor-activating effects of amphetamine have been reported to increase with repeated drug administration. Although the precise underlying mechanisms for this behavioral sensitization effect remain unknown, many investigators have suggested a role for the mesolimbic dopaminergic system that emanates from cell bodies in the ventral tegmental area (VTA) of the midbrain. To test this hypothesis, the present study examined the effects of repeated electrical stimulation of the VTA (in place of repeated amphetamine administration) on the hyperlocomotor actions of d-amphetamine. Locomotor activity induced by 0.75 mg/kg SC amphetamine was assessed during two 90-min tests, one before and one after a 14-day treatment regimen during which animals experienced daily 15-min sessions of intracranial VTA stimulation. Each session involved the delivery of 600 trains of 0.5 s 60-Hz sine-wave stimulation applied at one of four intensities: 0, 15, 30, or 45 microA. An additional comparison group of rats self-administered 30 microA of VTA stimulation. Data analysis revealed that both the self-stimulation and the high current groups were reliably more active posttreatment compared to pretreatment. No such sensitization-like effects were observed in any of the other treatment groups. These results are consistent with the hypothesis that repeated activation of VTA neurons can produce a sensitization to the behavioral effects of d-amphetamine.
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.
Neuroscience Letters, 1986
neurotensin ventral tegmental area dopamine locomotor activity amphetamine M icroinjections of neurotensin (NT) into the ventral tegmental area (VTA) of the rat increases locomotor activity. This effect on locomotion is potentiated by daily infustions of NT: in contrast a different injection schedule, i.e. every 48 h, had no such effect. In addition, daily NT injections in the VTA do not alter the locomotor response to a relatively low dose (0.5 mg/kg) of D-amphetamine. These results provide further evidence that NT can modulate the mesolimbic dopamine pathway. The putative peptide neurotransmitter neurotensin (NT) is known to be heterogeneously distributed within the central nervous system (CNS) of many mammals [I 7]. Furthermore, high concentrations of NT-like immunoreactivity have been located in areas rich in dopamine (DA) cell bodies and terminals [14, 16, 20]. Colocalization of DA and NT has also been reported in the mesolimbic and tuberoinfundibular DA systems [6, 7]. Recent studies have also provided compelling evidence that NT receptors are located on DA perikarya in the mesencephalon [18] and on certain DA terminals [5] as well. Moreover, iontophoretic application of NT in DA rich cell body areas such as the Am (ventral tegmental area; VTA) produces neuronal excitation [1]. In rats, microinjections of NT into the VTA increases locomotor activity [8-1 1]. This effect of NT is believed to occur via activation of the VTA-nucleus accumbens (NAS) DA pathway, an integral component of the mesolimbic DA system. This el= fect of NT after VTA injection is inhibited by pretreatment with the DA receptor antagonist haloperidol and also by 6-hydroxydopamine-induced lesions of DA terminals in the NAS [10]. Furthermore, infusion of NT into the VTA produces an increase in DA metabolites in the NAS and olfactory tubercles, indicative of mesolimbic DA-pathway activation [14]. These results, taken together, suggest a modulatory role of NT on the mesolimbic DA pathways.
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.
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.
Neuroscience, 2004
The pedunculopontine tegmental nucleus (PPTg) has long been suggested to have a role in reward-related behaviour, and there is particular interest in its possible role in drug reward systems. Previous work found increased i.v. self-administration (IVSA) of d-amphetamine following PPTg lesions when training had included both operant pre-training and priming injections. The present study examined the effect of excitotoxin lesions of the PPTg on d-amphetamine IVSA under three training conditions. Naive: no previous experience of d-amphetamine or operant responding. Pretrained: given operant training with food before lesion surgery took place. Primed: given single non-contingent d-amphetamine infusion (0.1 mg/0.l ml) at the start of each session. Rats in all conditions were given either ibotenate or phosphate buffer control lesions of the PPTg before d-amphetamine (0.1 mg/0.1 ml infusion) IVSA training took place. Rats received eight sessions of training under a fixed ratio (FR2) schedule of d-amphetamine IVSA, followed by four sessions under a progressive ratio (PR5) schedule.
Behavioural Brain Research, 1993
The experiments reported here have investigated the impact on re,,vard-rclated processes of Icsioning the basolateral amsgdala, ventral subiculum and pretimbic cortex which represent the major limhic sources of ",ffl'erents to the ventral striatum. The results showed that. while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. Howe,,er. there '.~ere important dil-I'erences between the eft'cots of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completel.,, abolished the loconlotor response to inlra-accumbens infusions of D-amphetamine, in addition to blocking the potentiative eftcot ot the same treatment em responding with conditioned reinforcement, l.esions of the basolateral am vgdala, b.v contrast, reduced the control over behaviour by a conditioned reinforcer, bt, t not the potentiation of that control by intra-accumbens D-amphetamine except at the highest dose. Moreover, the locomotor response to D-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected b,, amygdala lesions over the dose range blocked b5 ventral subiculum lesions. The results suggest a rather selective effect of am,,gdala-ventral striatal interactions ~n processes subserving conditioned reinforcement and a more fundamental influence of ventral st, biculum-venlral striatal interactions in mediating the psychomotor stimulant effects ol" D-amphetamine.