Purpose: The purpose of this work was to compare and analyse two clinically measurable beam quality specifiers, the half value layer (HVL) and the ratio of the doses at depths 2 cm and 5 cm (D2/D5) for a range of kilovoltage modalities, and to determine whether a practical, alternative and/or better correlation exists. Methods and materials: Four x-ray units were used: two Philips RT 250 units, a Pantak HF 420 operated up to 250 kV, and a D3300 Gulmay Medical unit operated up to 300 kV. As not all these units were equipped with an internal monitor chamber, a system was used where either the first measurement was repeated at the end of each series or an external monitor chamber was employed in order to ensure output constancy. A range of HVL’s were measured on each of the energies investigated on this work, which were used clinically. A calibrated 0.6 cc ionization chamber was used in a 30 cm x 30 cm x 30 cm water phantom to measure the absorbed dose to water at depths 2 cm and 5 cm in order to investigate D2/D5 as the alternative quality index. Results: The effectiveness of using a monitor chamber in the determination of HVL has been shown to be significant in this work where HVLs differed by up to 3%. Errors incurred from using HVL have been identified. This work verified that the ratio of doses at depths 2 cm and 5 cm in water could be applied as a kilovoltage beam quality specifier in the clinical environment at low and medium energies with a well defined FSD and field size. Conclusions: The use of D2/D5 as a tool to verify the beam quality index would simplify quality control in the clinical environment. Further work would have to be done to investigate other energies. Lower energies may require the use of shallower depths in order to improve accuracy and ensure a more clinically relevant setup.

The aim of the two studies presented here was to evaluate the effects of cocaine and mefloquine (MFQ) on γ-aminobutyric acid (GABA) and dopamine (DA) neurons in the ventral tegmental area (VTA). Cocaine: In vivo, lower doses of intravenous cocaine (0.25-0.5 mg/kg), or methamphetamine (METH), enhanced VTA GABA neuron firing rate via D2/D5 receptor activation. Higher cocaine doses (1.0-2.0 mg/kg) inhibited their firing rate. Cocaine and lidocaine inhibited the firing rate and spike discharges induced by stimulation of the internal capsule (ICPSDs) at dose levels 0.25-2 mg/kg (IC50 1.2 mg/kg), but neither DA nor METH reduced ICPSDs. In VTA GABA neurons in vitro, cocaine reduced (IC50 13 µM) current-evoked spikes and sodium currents in a use-dependent manner. In VTA DA neurons, cocaine reduced IPSCs (IC50 13 µM), increased IPSC paired-pulse facilitation, and decreased sIPSC frequency, without affecting mIPSC frequency or amplitude. These findings suggest cocaine reduces activity-dependent GABA release on DA neurons in the VTA, and that cocaine's use-dependent blockade of VTA GABA neuron voltage-sensitive sodium channels (VSSCs) may synergize with its DAT inhibiting properties to enhance mesolimbic DA transmission implicated in cocaine reinforcement. Mefloquine: Mefloquine (MFQ) is an anti-malarial agent, Connexin-36 (Cx36) gap junction blocker, 5-HT3 antagonist, and calcium ionophore. Mounting evidence of a Cx36-mediated VTA GABA neuron syncytium suggests MFQ-related dysphoria may attribute to its gap junction blocking effects on VTA synaptic homeostasis. We observed that MFQ (25 µM) increased DA neuron spontaneous IPSC frequency 6 fold, and mIPSC 3 fold. Carbenoxolone (CBX, 100 µM) only increased sIPSC frequency 2 fold, and did not affect DA mIPSC frequency. Ondansetron did not mimic MFQ. Additionally, MFQ did not affect VTA DA evoked IPSC paired pulse ratio (PPR). However, Mefloquine did induce a 3.5 fold increase in bath-applied GABA current. Remarkably, MFQ did not affect VTA GABA neuron inhibition. At VTA DA neuron excitatory synapses MFQ increased sEPSC frequency in-part due to an increase in the AMPA/NMDA ratio. These finding suggest MFQ alters VTA synapses differentially depending on neuron and synapse type, and that these alterations appear to involve MFQ's gap junction blocking and calcium ionophore actions.