Intracerebral Baclofen Administration Decreases Amphetamine-Induced Behavior and Neuropeptide Gene Expression in the Striatum

Abstract

In a previous study, systemic administration of the GABA B receptor agonist, R-( þ )-baclofen (2.5 mg/kg, i.p.) blocked acute amphetamine (2.5 mg/kg, i.p.)-induced rearing and neuropeptide (preprodynorphin (PPD), preprotachykinin (PPT), preproenkephalin (PPE), and secretogranin II (SGII)) mRNA expression in the striatum (Zhou et al, 2004). The purpose of the present study was to investigate the site(s) of action of these baclofen effects in the dorsal and ventral striatal circuitries. Infusion of baclofen (75 ng/side) into the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NA), caudate-putamen (Cpu), or medial prefrontal cortex (mPFC) had no effect on behavioral activity in saline-treated rats habituated to a photocell apparatus. However, intra-VTA infusion of baclofen (75 ng/ side) completely blocked, whereas intra-NA and intra-SN infusion of baclofen attenuated, amphetamine-induced vertical activity without affecting amphetamine-induced total distance traveled. In contrast, intramedial PFC and intra-CPu infusion of baclofen had no effect on behavioral activity in amphetamine-treated rats. Infusion of baclofen into the VTA, NA, or SN decreased amphetamine-induced neuropeptide gene expression in the striatum. These results indicate that GABA B receptor stimulation within the ventral striatal circuitry is involved in mediating acute amphetamine-induced behaviors and neuropeptide gene expression in the dorsal and ventral striatum. The present study provides information on the potential targets in the brain for baclofen in the initial behavioral and genomic response to amphetamine.

GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper

“…[53][54][55] Consistently, baclofen pretreatment completely inhibited the acute effect of amphetamine in mice bilaterally injected in the VTA with the control virus (Figure 5a). In contrast, although amphetamine administration further enhanced locomotor activity in mice injected with the AAV-PRAF2+GFP virus, baclofen pretreatment failed to abolish this effect, supporting the impairment of GABA B receptor inhibitory activity in this context (Figure 5b).…”

The role of nucleus accumbens shell GABA receptors on ventral tegmental area intracranial self-stimulation and a potential role for the 5-HT2Creceptor

“…Together, these data suggest that GABA A receptors in the rostral NAc shell play an inhibitory role in regulating VTA ICSS behaviour, while GABA B receptors are not of primary importance under the present experimental conditions, although they may be more involved in regulating rewardrelated behaviours in other brain areas such as the VTA (Willick and Kokkinidis, 1995;Zhou et al, 2005). This is in contrast to their proposed role in feeding and other rewardrelated behaviours, mentioned above, but is not inconsistent with a differential role for receptors across reward-related behaviours (see, for example, Backes and Hemby, 2008;Hayes et al, 2009c;Martin-Fardon et al, 2007).…”

Adolescent Toluene Inhalation in Rats Affects White Matter Maturation with the Potential for Recovery Following Abstinence

“…In line with this, altered ventral striatal dopamine activity and medial frontal cortical serotonergic activity [65] has been observed in Wistar rats with low rearing activity in a novel open field, however rearing activity normalises once novelty is removed following repeated exposure [56]. Furthermore, injections of glutamate into the core of the nucleus accumbens reduce rearing without changes to overall locomotion [66], while infusion of the gamma-aminobutyric acid B receptor agonist baclofen, is sufficient to inhibit amphetamine-induced increases in rearing activity [67]. Together, this suggests that several neurotransmitter systems influence behaviours mediating rearing activity, many if not all of which are affected by toluene [68], [69].…”